Is CFAP263 p.Arg124His (c.371G>A) pathogenic?

CFAP263 p.Arg124His (c.371G>A) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: likely benign (0.1824); Ultra-rare (popmax 0.0433%, amr).

How common is CFAP263 p.Arg124His (c.371G>A) in the general population?

CFAP263 p.Arg124His (c.371G>A) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

What do computational predictors say about CFAP263 p.Arg124His (c.371G>A)?

AlphaMissense predicts likely benign (score 0.1824) — an in-silico prediction, not a clinical call.

CFAP263 p.Arg124His

c.371G>A · rs147141699 · VCV2292180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1824 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1824	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.51	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 8.3	GERP 0.86, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	24.9	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 0.0433% Admixed American · 26/59,996 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00316% 51/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0433%	2,308
African / African-American	0.0214%	4,682
East Asian	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.000169%	590,019

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: CFAP263
Protein: p.Arg124His
Coding: c.371G>A
MANE Select: NM_014157
dbSNP: rs147141699
Type: single nucleotide variant
Location: chr16:58254140 (GRCh38)
Structure: AlphaFold pLDDT 83.57 · 1 PDB

Full CFAP263 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP263 p.Arg124Cys Uncertain significance ★ ⚠ same residue
CFAP263 p.Ala122Val Uncertain significance ★ ⚠ same type
CFAP263 p.Ala131Val Uncertain significance ★ ⚠ same type
CFAP263 p.Ala167Ser Uncertain significance ★ ⚠ same type
CFAP263 p.Ala371Thr Uncertain significance ★ ⚠ same type
CFAP263 p.Ala39Thr Uncertain significance ★ ⚠ same type
CFAP263 p.Arg116Gln Uncertain significance ★ ⚠ same type
CFAP263 p.Arg180His 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/cfap263-p-arg124his (accessed [today's date]).

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