Is CEP63 p.Arg191Gln (c.572G>A) pathogenic?

CEP63 p.Arg191Gln (c.572G>A) is classified Conflicting classifications of pathogenicity in CEP63 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-10). AlphaMissense: likely benign (0.1264); Rare (popmax 0.215%, amr).

How common is CEP63 p.Arg191Gln (c.572G>A) in the general population?

CEP63 p.Arg191Gln (c.572G>A) is rare (popmax 0.215%, amr) (gnomAD).

What do computational predictors say about CEP63 p.Arg191Gln (c.572G>A)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

CEP63 p.Arg191Gln

c.572G>A · rs529386244 · VCV434745

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.215%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -2.75	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 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	25.7	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 0.215% Admixed American · 129/60,014 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.00961% 155/1,613,714 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.215%	465
East Asian	0.0156%	6,409
South Asian	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.0064%	15,623
African / African-American	0.004%	24,983
European (non-Finnish)	0.000339%	294,939

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.Arg191Gln
Coding: c.572G>A
MANE Select: NM_001353108
dbSNP: rs529386244
Type: single nucleotide variant
Location: chr3:134545602 (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.Arg191Trp 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.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-arg191gln (accessed [today's date]).

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