Is CEP63 p.Ala275Pro (c.823G>C) pathogenic?

CEP63 p.Ala275Pro (c.823G>C) is classified Uncertain significance in CEP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.5597); Very rare (popmax 0.005%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP63 p.Ala275Pro (c.823G>C)?

CEP63 p.Ala275Pro (c.823G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP63 p.Ala275Pro (c.823G>C) in the general population?

CEP63 p.Ala275Pro (c.823G>C) is very rare (popmax 0.005%, nfe) (gnomAD).

What do computational predictors say about CEP63 p.Ala275Pro (c.823G>C)?

AlphaMissense predicts ambiguous (score 0.5597) — an in-silico prediction, not a clinical call.

CEP63 p.Ala275Pro

c.823G>C · VCV3490865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5597	ambiguous
REVEL	0.099	moderately benign-leaning
SaProt	LLR -11.92	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 0.96	GERP -3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	16.67	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 0.005% European (non-Finnish) · 59/1,179,922 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00372% 60/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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: CEP63
Protein: p.Ala275Pro
Coding: c.823G>C
MANE Select: NM_001353108
Type: single nucleotide variant
Location: chr3:134546182 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.95 · 4 PDB

Full CEP63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP63 p.Ala275Thr Uncertain significance ★ ⚠ same residue
CEP63 p.Arg215Trp Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg46His Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg474His Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg57His Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn301Ile Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn633Asp Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn633Ser Uncertain significance ★★ ⚠ same condition

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/cep63-p-ala275pro (accessed [today's date]).

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