Is CFAP251 p.Val899Ile (c.2695G>A) pathogenic?

CFAP251 p.Val899Ile (c.2695G>A) is classified Likely benign in CFAP251 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0625); Ultra-rare (popmax 0.033%, mid).

How common is CFAP251 p.Val899Ile (c.2695G>A) in the general population?

CFAP251 p.Val899Ile (c.2695G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CFAP251 p.Val899Ile (c.2695G>A)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

CFAP251 p.Val899Ile

c.2695G>A · VCV4652797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.099	GERP -2.1, phastCons 0.003
Regional constraint	o/e 0.93	unconstrained · MANE · 82 kb · p 0.0061 · regional, not allelic
Overall
CADD	6.159	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00161% 26/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0176%	5,691
African / African-American	0.00133%	75,042
European (non-Finnish)	0.000593%	168,530

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: CFAP251
Protein: p.Val899Ile
Coding: c.2695G>A
MANE Select: NM_144668
Type: single nucleotide variant
Location: chr12:121968093 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 899: a UniProt-annotated variant site (in spgf33)

Full CFAP251 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP251 p.Arg267Ter Pathogenic ★★ same type
CFAP251 p.Glu111Ter Pathogenic/Likely pathogenic ★★ same type
CFAP251 c.-20-20T>C Benign ★★ same type
CFAP251 p.Arg417Gln Benign ★★ same type
CFAP251 p.Ile970= Likely benign ★★ same type
CFAP251 p.Val307Ile Benign ★★ ⚠ same type
CFAP251 c.-20-2A>C Likely pathogenic ★ same type
CFAP251 p.Gln129Ter Likely 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/cfap251-p-val899ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown