Is CEP63 p.Tyr321Phe (c.962A>T) pathogenic?

CEP63 p.Tyr321Phe (c.962A>T) is classified Likely benign in CEP63 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-24). AlphaMissense: likely benign (0.0958); Rare (popmax 0.239%, eas).

How common is CEP63 p.Tyr321Phe (c.962A>T) in the general population?

CEP63 p.Tyr321Phe (c.962A>T) is rare (popmax 0.239%, eas) (gnomAD).

What do computational predictors say about CEP63 p.Tyr321Phe (c.962A>T)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

CEP63 p.Tyr321Phe

c.962A>T · rs367734078 · VCV782810

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.239%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -5.87	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 0.35	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	0.707	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 0.239% East Asian · 107/44,848 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.01% 162/1,613,714 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.239%	419
Remaining individualsnot grpmax-eligible	0.072%	1,389
Admixed American	0.00333%	30,008
South Asian	0.0022%	45,537
European (non-Finnish)	0.000509%	196,611

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.Tyr321Phe
Coding: c.962A>T
MANE Select: NM_001353108
dbSNP: rs367734078
Type: single nucleotide variant
Location: chr3:134547367 (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

Similar variants

CEP63 p.Tyr321= Likely benign ★ same residue
CEP63 c.1067+2T>C Likely pathogenic ★★ same type
CEP63 c.790-2A>G Likely pathogenic ★★ same type
CEP63 p.Arg150His Uncertain significance ★★ ⚠ same type
CEP63 p.Arg215Trp Uncertain significance ★★ ⚠ same type
CEP63 p.Arg229Cys Uncertain significance ★★ ⚠ same type
CEP63 p.Arg312Gln Uncertain significance ★★ ⚠ same type
CEP63 p.Arg46His 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/cep63-p-tyr321phe (accessed [today's date]).

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