PRRC2C p.Phe252Ile
c.754T>A · VCV4145561
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00339%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.197 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 1.19 | unconstrained · MANE · 7,677 bp · p 0.0079 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00339%
Admixed American · 2/58,984 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.00185%
29/1,567,788 alleles · very rare
exomes 29/1,415,492 · genomes 0/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00339% | 29,492 |
| European (non-Finnish) | 0.00235% | 42,501 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PRRC2C
- Protein
- p.Phe252Ile
- Coding
- c.754T>A
- MANE Select
- NM_001387844
- Type
- single nucleotide variant
- Location
- chr1:171522180 (GRCh38)
- Gene constraint
- LOEUF 0.287 · pLI 1.00 (gnomAD)
Similar variants
- PRRC2C c.1055+2T>C Uncertain significance ★ same type
- PRRC2C p.Ala104Thr Uncertain significance ★ same type
- PRRC2C p.Ala1120Thr Uncertain significance ★ same type
- PRRC2C p.Ala1762Ser Uncertain significance ★ same type
- PRRC2C p.Ala1774Ser Uncertain significance ★ same type
- PRRC2C p.Ala1785Val Uncertain significance ★ same type
- PRRC2C p.Ala1927Thr Uncertain significance ★ same type
- PRRC2C p.Ala1930Val Uncertain significance ★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prrc2c-p-phe252ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown