Is CEP63 p.Arg229Cys (c.685C>T) pathogenic?

CEP63 p.Arg229Cys (c.685C>T) is classified Uncertain significance in CEP63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-20). AlphaMissense: likely benign (0.2883); Very rare (popmax 0.00401%, afr).

How common is CEP63 p.Arg229Cys (c.685C>T) in the general population?

CEP63 p.Arg229Cys (c.685C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CEP63 p.Arg229Cys (c.685C>T)?

AlphaMissense predicts likely benign (score 0.2883) — an in-silico prediction, not a clinical call.

CEP63 p.Arg229Cys

c.685C>T · rs772271443 · VCV493374

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2883	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -9.68	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	33.0	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 0.00401% African / African-American · 3/74,886 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,613,882 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,962
Admixed American	0.00333%	29,997
East Asian	0.00223%	44,868
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000254%	393,326

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.Arg229Cys
Coding: c.685C>T
MANE Select: NM_001353108
dbSNP: rs772271443
Type: single nucleotide variant
Location: chr3:134545715 (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.Arg229His Uncertain significance ★ ⚠ 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.Arg312Gln Uncertain significance ★★ ⚠ same type
CEP63 p.Arg46His Uncertain significance ★★ ⚠ same type
CEP63 p.Arg474His 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-arg229cys (accessed [today's date]).

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