Is CFAP263 p.Arg124Cys (c.370C>T) pathogenic?

CFAP263 p.Arg124Cys (c.370C>T) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.3596); Ultra-rare (popmax 0.016%, nfe).

How common is CFAP263 p.Arg124Cys (c.370C>T) in the general population?

CFAP263 p.Arg124Cys (c.370C>T) is ultra-rare (popmax 0.016%, nfe) (gnomAD).

What do computational predictors say about CFAP263 p.Arg124Cys (c.370C>T)?

AlphaMissense predicts ambiguous (score 0.3596) — an in-silico prediction, not a clinical call.

CFAP263 p.Arg124Cys

c.370C>T · rs200282611 · VCV3235467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3596 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3596	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.8, phastCons 0.91
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	22.6	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 0.016% European (non-Finnish) · 189/1,180,038 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.0126% 204/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.016%	6,244
African / African-American	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.00329%	30,363

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.Arg124Cys
Coding: c.370C>T
MANE Select: NM_014157
dbSNP: rs200282611
Type: single nucleotide variant
Location: chr16:58254139 (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.Arg124His 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-arg124cys (accessed [today's date]).

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