Is CFAP251 p.Val287Met (c.859G>A) pathogenic?

CFAP251 p.Val287Met (c.859G>A) is classified Uncertain significance in CFAP251 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.1741); Very rare (popmax 0.00229%, sas).

How common is CFAP251 p.Val287Met (c.859G>A) in the general population?

CFAP251 p.Val287Met (c.859G>A) is very rare (popmax 0.00229%, sas) (gnomAD).

What do computational predictors say about CFAP251 p.Val287Met (c.859G>A)?

AlphaMissense predicts likely benign (score 0.1741) — an in-silico prediction, not a clinical call.

CFAP251 p.Val287Met

c.859G>A · VCV3832267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1741	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -8.18	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 3.7	GERP -0.57, phastCons 0.95
Regional constraint	o/e 0.93	unconstrained · MANE · 82 kb · p 0.0061 · regional, not allelic
Overall
CADD	16.72	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% South Asian · 2/87,252 alleles

Filtering AF 0.000381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000142%

Overall 0.000439% 7/1,593,616 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00229%	43,626
African / African-American	0.00135%	73,862
European (non-Finnish)	0.000341%	292,834

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.Val287Met
Coding: c.859G>A
MANE Select: NM_144668
Type: single nucleotide variant
Location: chr12:121931857 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 287: 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-val287met (accessed [today's date]).

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