Is CFAP263 p.Ser70Ala (c.208T>G) pathogenic?

CFAP263 p.Ser70Ala (c.208T>G) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.0592); Ultra-rare (popmax 0.0223%, eas).

How common is CFAP263 p.Ser70Ala (c.208T>G) in the general population?

CFAP263 p.Ser70Ala (c.208T>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about CFAP263 p.Ser70Ala (c.208T>G)?

AlphaMissense predicts likely benign (score 0.0592) — an in-silico prediction, not a clinical call.

CFAP263 p.Ser70Ala

c.208T>G · VCV3266426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0592 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0592	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.30	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 -1.8	GERP -2.7
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	0.026	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 0.0223% East Asian · 10/44,900 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00651% 105/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
Middle Eastern	0.0164%	6,082
Admixed American	0.00833%	12,002
European (non-Finnish)	0.00703%	14,215
Finnishnot grpmax-eligible	0.00469%	21,341
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0011%	91,088

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.Ser70Ala
Coding: c.208T>G
MANE Select: NM_014157
Type: single nucleotide variant
Location: chr16:58252833 (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-ser70ala (accessed [today's date]).

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