CFAP99 p.Arg278Gln
c.833G>A · VCV4653022
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0499%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor loss, 37 bp away · masked 0 · deltas |
| Pangolin | Δ0.22 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.49 | GERP -3.9 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 36 kb · p 0.016 · regional, not allelic |
| Overall | ||
| CADD | 11.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0499%
Middle Eastern · 3/6,008 alleles
Filtering AF
0.0192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0161%
Overall
0.00762%
117/1,535,880 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0499% | 2,003 |
| African / African-American | 0.0288% | 3,477 |
| European (non-Finnish) | 0.0075% | 13,336 |
| Admixed American | 0.00589% | 16,991 |
| Remaining individualsnot grpmax-eligible | 0.005% | 19,996 |
| South Asian | 0.00119% | 84,066 |
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.Arg278Gln
- Coding
- c.833G>A
- MANE Select
- NM_001193282
- Type
- single nucleotide variant
- Location
- chr4:2450984 (GRCh38)
- Gene constraint
- LOEUF 1.203 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.28
Similar variants
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- 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-arg278gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown