CFAP99 p.Lys233Arg
c.698A>G · rs753453203 · VCV2594408
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00785%, amr)
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 2.7 | GERP 0.73, phastCons 1 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 36 kb · p 0.016 · regional, not allelic |
| Overall | ||
| CADD | 13.76 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00785%
Admixed American · 4/50,980 alleles
Filtering AF
0.00263%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00204%
Overall
0.0028%
43/1,536,034 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00785% | 12,745 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,000 |
| European (non-Finnish) | 0.00314% | 31,859 |
| African / African-American | 0.00137% | 73,038 |
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.Lys233Arg
- Coding
- c.698A>G
- MANE Select
- NM_001193282
- dbSNP
- rs753453203
- Type
- single nucleotide variant
- Location
- chr4:2449725 (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-lys233arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown