# NM_001387844.1(PRRC2C):c.150C>T (p.Val50=)

https://sugi.bio/variant/prrc2c-p-val50

## Summary

**PRRC2C p.Val50= (c.150C>T)** is classified **Likely benign** in PRRC2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Ultra-rare (popmax 0.0331%, nfe).

**At a glance:** Likely benign · review: Single submitter · 1 submitter · ultra-rare (popmax 0.0331%, nfe)

## For patients & families {#patients}

This is a change in the PRRC2C gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PRRC2C](https://sugi.bio/atlas/gene/PRRC2C/) |
| Protein change (HGVS p.) | p.Val50= |
| Coding change (HGVS c.) | c.150C>T |
| MANE Select transcript | [NM_001387844](https://www.ncbi.nlm.nih.gov/nuccore/NM_001387844) |
| Variant type | single nucleotide variant |
| Location | chr1:171513032-171513032 (GRCh38) |
| ClinVar | [VCV3388016](https://www.ncbi.nlm.nih.gov/clinvar/variation/3388016/) |

**All HGVS expressions:** `NC_000001.10:g.171482171C>T`, `NC_000001.11:g.171513032C>T`, `NM_001387844.1:c.150C>T`, `NM_015172.4:c.144C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 2.363, GERP -3.46, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 12.58**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.28 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.0331%** (nfe) · FAF95 0.0303% · FAF99 0.0293% · 390/1,179,532 in the highest group · 1,157/1,612,924 alleles overall — ultra-rare (popmax 0.0331%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Ashkenazi Jewish (not grpmax-eligible) | 2.23% | 45 |
| Amish (not grpmax-eligible) | 0.548% | 182 |
| Remaining individuals (not grpmax-eligible) | 0.146% | 686 |
| European (non-Finnish) (grpmax) | 0.0331% | 3,024 |
| Admixed American | 0.0117% | 8,549 |
| Finnish (not grpmax-eligible) | 0.00313% | 31,992 |
| East Asian | 0.00223% | 44,866 |
| African / African-American | 0.00134% | 74,852 |

Ashkenazi Jewish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**PRRC2C** population constraint: LOEUF 0.287, pLI 1, missense-Z 2.4844. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **50** lies in the 'disordered' region.

## What this gene does {#gene-function}

*Describes the biological roles of PRRC2C (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** PRRC2C's established molecular role includes RNA binding. p.Val50= falls in the disordered region.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA binding.

**Biological process:** cytoplasmic stress granule assembly.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-10-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2024-10-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related PRRC2C variant pages (same residue, condition, or type): [PRRC2C c.1055+2T>C](/variant/prrc2c-c-1055-plus-2t-c), [PRRC2C p.Ala104Thr](/variant/prrc2c-p-ala104thr), [PRRC2C p.Ala1120Thr](/variant/prrc2c-p-ala1120thr), [PRRC2C p.Ala1762Ser](/variant/prrc2c-p-ala1762ser), [PRRC2C p.Ala1774Ser](/variant/prrc2c-p-ala1774ser), [PRRC2C p.Ala1785Val](/variant/prrc2c-p-ala1785val), [PRRC2C p.Ala1927Thr](/variant/prrc2c-p-ala1927thr), [PRRC2C p.Ala1930Val](/variant/prrc2c-p-ala1930val).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3388016). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*