# NM_001370752.1(BTD):c.1029C>T (p.Val343=)

https://sugi.bio/variant/btd-p-val343

## Summary

**BTD p.Val343= (c.1029C>T)** is classified **Likely benign** in BTD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Absent from gnomAD v4.1.

**At a glance:** Likely benign · review: Single submitter · rsID rs2073760945 · 1 submitter · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the BTD 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 | [BTD](https://sugi.bio/atlas/gene/BTD/) |
| Protein change (HGVS p.) | p.Val343= |
| Coding change (HGVS c.) | c.1029C>T |
| MANE Select transcript | [NM_001349278](https://www.ncbi.nlm.nih.gov/nuccore/NM_001349278) (variant reported on NM_001370752) |
| dbSNP | [rs2073760945](https://www.ncbi.nlm.nih.gov/snp/rs2073760945/) |
| Variant type | single nucleotide variant |
| Location | chr3:15721783-15721783 (GRCh38) |
| ClinVar | [VCV2653604](https://www.ncbi.nlm.nih.gov/clinvar/variation/2653604/) |

**All HGVS expressions:** `NC_000003.11:g.15763290C>T`, `NC_000003.12:g.15721783C>T`, `NG_008019.3:g.125433C>T`, `NM_001195098.1:c.232-656G>A`, `NM_001195099.2:c.232-656G>A`, `NM_001349277.2:c.793-656G>A`, `NM_001349278.2:c.784-656G>A`, `NM_001349279.2:c.685-656G>A`, `NM_001349280.1:c.526-656G>A`, `NM_001349281.2:c.526-656G>A`, `NM_001349282.2:c.526-656G>A`, `NM_001349283.2:c.232-656G>A`, `NM_001370752.1:c.1029C>T`, `NM_001407379.1:c.1029C>T`, `NM_015199.4:c.694-656G>A`

## 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 -4.116, GERP -0.557 — fast-evolving / accelerated position
- CADD: **PHRED 0.715**. 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: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-07-01.

**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 | 2022-07-01 |

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

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 2653604). 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.*