Is CEP63 p.Met413Ile (c.1239G>A) pathogenic?

CEP63 p.Met413Ile (c.1239G>A) is classified Uncertain significance in CEP63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). AlphaMissense: likely pathogenic (0.9018); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP63 p.Met413Ile (c.1239G>A)?

CEP63 p.Met413Ile (c.1239G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEP63 p.Met413Ile (c.1239G>A) in the general population?

CEP63 p.Met413Ile (c.1239G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CEP63 p.Met413Ile (c.1239G>A)?

AlphaMissense predicts likely pathogenic (score 0.9018) — an in-silico prediction, not a clinical call.

CEP63 p.Met413Ile

c.1239G>A · VCV4226439

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9018	likely pathogenic · top 4% in CEP63
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	27.2	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 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,562 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,074
European (non-Finnish)	0.000254%	393,218

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.Met413Ile
Coding: c.1239G>A
MANE Select: NM_001353108
Type: single nucleotide variant
Location: chr3:134550119 (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.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
CEP63 p.Gln645Glu 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-met413ile (accessed [today's date]).

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