PRRC2C p.Pro428Ser
c.1282C>T · rs1386678705 · VCV2360730
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.05 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -0.17, phastCons 0.45 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 18 kb · p 0.043 · regional, not allelic |
| Overall | ||
| CADD | 15.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
Middle Eastern · 4/6,058 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.000372%
6/1,613,520 alleles · ultra-rare
exomes 6/1,461,270 · genomes 0/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.066% | 1,514 |
| European (non-Finnish) | 0.00017% | 589,863 |
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.Pro428Ser
- Coding
- c.1282C>T
- MANE Select
- NM_001387844
- dbSNP
- rs1386678705
- Type
- single nucleotide variant
- Location
- chr1:171532370 (GRCh38)
- Gene constraint
- LOEUF 0.287 · pLI 1.00 (gnomAD)
- Residue 428
- the 'disordered' region
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-pro428ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown