Is CFAP157 p.Gln468Pro (c.1403A>C) pathogenic?

CFAP157 p.Gln468Pro (c.1403A>C) is classified Uncertain significance in CFAP157 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0746); Very rare (popmax 0.00133%, afr).

How common is CFAP157 p.Gln468Pro (c.1403A>C) in the general population?

CFAP157 p.Gln468Pro (c.1403A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CFAP157 p.Gln468Pro (c.1403A>C)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

CFAP157 p.Gln468Pro

c.1403A>C · VCV4001390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -4.75	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 -0.2	GERP -3.1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,870 bp · p 0.054 · regional, not allelic
Overall
CADD	0.459	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 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000657% 1/152,192 alleles · very rare

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: CFAP157
Protein: p.Gln468Pro
Coding: c.1403A>C
MANE Select: NM_001012502
Type: single nucleotide variant
Location: chr9:127713118 (GRCh38)
Gene constraint: LOEUF 0.998 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.75

Full CFAP157 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP157 p.Ala121Val Uncertain significance ★ ⚠ same type
CFAP157 p.Ala365Val Uncertain significance ★ ⚠ same type
CFAP157 p.Ala420Glu Uncertain significance ★ ⚠ same type
CFAP157 p.Arg155Gln Uncertain significance ★ ⚠ same type
CFAP157 p.Arg155Trp Uncertain significance ★ ⚠ same type
CFAP157 p.Arg308His Uncertain significance ★ ⚠ same type
CFAP157 p.Arg317Thr Uncertain significance ★ ⚠ same type
CFAP157 p.Arg348Trp 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/cfap157-p-gln468pro (accessed [today's date]).

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