CFAP99 p.Ala422Val
c.1265C>T · VCV4227257
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.018 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.2 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 36 kb · p 0.016 · regional, not allelic |
| Overall | ||
| CADD | 0.247 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
East Asian · 18/40,910 alleles
Filtering AF
0.0284%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0234%
Overall
0.00443%
68/1,535,810 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.044% | 2,273 |
| South Asian | 0.00833% | 12,004 |
| Admixed American | 0.00785% | 12,743 |
| Remaining individualsnot grpmax-eligible | 0.005% | 19,997 |
| European (non-Finnish) | 0.00296% | 33,731 |
| African / African-American | 0.00273% | 36,579 |
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
- CFAP99
- Protein
- p.Ala422Val
- Coding
- c.1265C>T
- MANE Select
- NM_001193282
- Type
- single nucleotide variant
- Location
- chr4:2458826 (GRCh38)
- Gene constraint
- LOEUF 1.203 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.28
Similar variants
- CFAP99 p.Ala255Thr Uncertain significance ★ same type
- CFAP99 p.Ala307Thr Uncertain significance ★ same type
- CFAP99 p.Ala366Thr Uncertain significance ★ same type
- CFAP99 p.Ala369Gly Uncertain significance ★ same type
- CFAP99 p.Ala396Val Uncertain significance ★ same type
- CFAP99 p.Ala423Thr Uncertain significance ★ same type
- CFAP99 p.Ala428Thr Uncertain significance ★ same type
- CFAP99 p.Ala450Ser 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/cfap99-p-ala422val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown