RPGRIP1 p.Ala641=
c.1923C>T · VCV4920901
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00314%, nfe)
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 -0.42 | GERP -0.048, phastCons 0.071 |
| Overall | ||
| CADD | 4.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00314%
European (non-Finnish) · 37/1,179,914 alleles
Filtering AF
0.00231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00242%
39/1,613,930 alleles · very rare
exomes 38/1,461,712 · genomes 1/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00314% | 31,890 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,468 |
| African / African-American | 0.00133% | 74,926 |
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
- RPGRIP1
- Protein
- p.Ala641=
- Coding
- c.1923C>T
- MANE Select
- NM_020366
- Type
- single nucleotide variant
- Location
- chr14:21324778 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.60 · 1 PDB
Similar variants
- RPGRIP1 p.Ala641Thr Uncertain significance ★★ ⚠ same residue
- RPGRIP1 c.1467+1G>A Pathogenic/Likely pathogenic ★★ same type
- RPGRIP1 c.1468-2A>G Pathogenic/Likely pathogenic ★★ same type
- RPGRIP1 c.218+1G>T Likely pathogenic ★★ same type
- RPGRIP1 c.2367+1G>A Pathogenic ★★ same type
- RPGRIP1 c.2368-2A>G Pathogenic/Likely pathogenic ★★ same type
- RPGRIP1 c.2711-2A>G Pathogenic ★★ same type
- RPGRIP1 c.2895+1G>T Pathogenic ★★ 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/rpgrip1-p-ala641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown