Is CFAP263 p.Phe222Val (c.664T>G) pathogenic?

CFAP263 p.Phe222Val (c.664T>G) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.6469); Very rare (popmax 0.00263%, nfe).

How common is CFAP263 p.Phe222Val (c.664T>G) in the general population?

CFAP263 p.Phe222Val (c.664T>G) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about CFAP263 p.Phe222Val (c.664T>G)?

AlphaMissense predicts likely pathogenic (score 0.6469) — an in-silico prediction, not a clinical call.

CFAP263 p.Phe222Val

c.664T>G · rs901109770 · VCV3235471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6469	likely pathogenic
REVEL	0.392	indeterminate
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	22.9	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 0.00263% European (non-Finnish) · 31/1,179,082 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00192% 31/1,612,852 alleles · very rare exomes 29/1,460,694 · genomes 2/152,158 · joint denominator

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.Phe222Val
Coding: c.664T>G
MANE Select: NM_014157
dbSNP: rs901109770
Type: single nucleotide variant
Location: chr16:58262421 (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.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
CFAP263 p.Arg124His 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-phe222val (accessed [today's date]).

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