Is CFAP251 p.Leu499Phe (c.1497G>T) pathogenic?

CFAP251 p.Leu499Phe (c.1497G>T) is classified Uncertain significance in CFAP251 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: ambiguous (0.4195); Absent from gnomAD v4.1.

How common is CFAP251 p.Leu499Phe (c.1497G>T) in the general population?

CFAP251 p.Leu499Phe (c.1497G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP251 p.Leu499Phe (c.1497G>T)?

AlphaMissense predicts ambiguous (score 0.4195) — an in-silico prediction, not a clinical call.

CFAP251 p.Leu499Phe

c.1497G>T · rs1881636186 · VCV2480138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4195 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4195	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -9.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.81, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 82 kb · p 0.0061 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP251
Protein: p.Leu499Phe
Coding: c.1497G>T
MANE Select: NM_144668
dbSNP: rs1881636186
Type: single nucleotide variant
Location: chr12:121954296 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 499: 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-leu499phe (accessed [today's date]).

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