Is CFAP263 p.Arg190Ser (c.568C>A) pathogenic?

CFAP263 p.Arg190Ser (c.568C>A) is classified Uncertain significance in CFAP263 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: ambiguous (0.3469); Very rare (popmax 0.00675%, amr).

How common is CFAP263 p.Arg190Ser (c.568C>A) in the general population?

CFAP263 p.Arg190Ser (c.568C>A) is very rare (popmax 0.00675%, amr) (gnomAD).

What do computational predictors say about CFAP263 p.Arg190Ser (c.568C>A)?

AlphaMissense predicts ambiguous (score 0.3469) — an in-silico prediction, not a clinical call.

CFAP263 p.Arg190Ser

c.568C>A · VCV3491253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00675%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3469	ambiguous
REVEL	0.208	benign-leaning
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.47 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.005	GERP -0.93, phastCons 0.71
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	14.8	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 0.00675% Admixed American · 4/59,218 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000314% 5/1,591,672 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00675%	14,805
Remaining individualsnot grpmax-eligible	0.00162%	61,726

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.Arg190Ser
Coding: c.568C>A
MANE Select: NM_014157
Type: single nucleotide variant
Location: chr16:58259875 (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.Arg190His 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-arg190ser (accessed [today's date]).

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