Is CEP63 p.Ser41Cys (c.122C>G) pathogenic?

CEP63 p.Ser41Cys (c.122C>G) is classified Uncertain significance in CEP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.1529); Ultra-rare (popmax 0.0615%, nfe).

How common is CEP63 p.Ser41Cys (c.122C>G) in the general population?

CEP63 p.Ser41Cys (c.122C>G) is ultra-rare (popmax 0.0615%, nfe) (gnomAD).

What do computational predictors say about CEP63 p.Ser41Cys (c.122C>G)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

CEP63 p.Ser41Cys

c.122C>G · rs146294786 · VCV1351640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0615%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -8.29	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 5.9	GERP 0.25, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	27.3	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 0.0615% European (non-Finnish) · 726/1,179,814 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0563%

Overall 0.0491% 793/1,613,502 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0615%	1,625
South Asian	0.034%	2,938
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Middle Eastern	0.0164%	6,080
Admixed American	0.0133%	7,496
African / African-American	0.00802%	12,469
Finnishnot grpmax-eligible	0.00313%	31,978

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.Ser41Cys
Coding: c.122C>G
MANE Select: NM_001353108
dbSNP: rs146294786
Type: single nucleotide variant
Location: chr3:134507186 (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

KY p.Leu41= 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-ser41cys (accessed [today's date]).

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