Is CFAP263 p.His148Pro (c.443A>C) pathogenic?

CFAP263 p.His148Pro (c.443A>C) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: ambiguous (0.4246); Very rare (popmax 0.00769%, sas).

How common is CFAP263 p.His148Pro (c.443A>C) in the general population?

CFAP263 p.His148Pro (c.443A>C) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CFAP263 p.His148Pro (c.443A>C)?

AlphaMissense predicts ambiguous (score 0.4246) — an in-silico prediction, not a clinical call.

CFAP263 p.His148Pro

c.443A>C · VCV4652805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4246 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4246	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -13.28	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 5.9	GERP 0.41, phastCons 0.67
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	13.47	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 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000616% 9/1,461,726 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
European (non-Finnish)	0.00017%	589,950

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.His148Pro
Coding: c.443A>C
MANE Select: NM_014157
Type: single nucleotide variant
Location: chr16:58258420 (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.His148Leu 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.Arg124Cys 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-his148pro (accessed [today's date]).

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