CA4 p.Pro287=
c.861G>A · rs962446098 · VCV1103709
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0224%, eas)
Conditions
1
inherited retinal dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -2.6 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0224%
East Asian · 10/44,708 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0092%
Overall
0.00155%
25/1,609,572 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0224% | 4,471 |
| African / African-American | 0.00535% | 18,707 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,238 |
| South Asian | 0.0011% | 90,540 |
| European (non-Finnish) | 0.000764% | 130,916 |
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
- CA4
- Protein
- p.Pro287=
- Coding
- c.861G>A
- MANE Select
- NM_000717
- dbSNP
- rs962446098
- Type
- single nucleotide variant
- Location
- chr17:60159346 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
Similar variants
- CA4 p.Pro287Leu Uncertain significance ★ ⚠ same residue
- CA4 p.Asp268Asn Uncertain significance ★★ ⚠ same condition
- CA4 p.Ala164= Benign/Likely benign ★★ same condition
- CA4 p.Asn177Lys Benign/Likely benign ★★ same condition
- CA4 p.Asp161= Likely benign ★★ same condition
- CA4 p.Lys145= Benign/Likely benign ★★ same condition
- CA4 p.Ser119= Benign/Likely benign ★★ same condition
- CA4 p.Cys229Ter Likely pathogenic ★ same condition
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/ca4-p-pro287 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown