Is CEP63 p.Gln537fs (c.1608dup) pathogenic?

CEP63 p.Gln537fs (c.1608dup) is classified Pathogenic in CEP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). Very rare (popmax 0.00267%, afr).

How common is CEP63 p.Gln537fs (c.1608dup) in the general population?

CEP63 p.Gln537fs (c.1608dup) is very rare (popmax 0.00267%, afr) (gnomAD).

CEP63 p.Gln537fs

c.1608dup · rs756469612 · VCV1924575

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP 0.93, phastCons 1
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,858 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000992% 16/1,613,500 alleles · very rare exomes 15/1,461,534 · genomes 1/151,966 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,429
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.0011%	90,752

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.Gln537fs
Coding: c.1608dup
MANE Select: NM_001353108
dbSNP: rs756469612
Type: Duplication
Location: chr3:134558276 (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 c.1673+12dup Benign/Likely benign ★★ same type
CEP63 p.Asn385fs Pathogenic ★ same type
CEP63 p.Lys62delinsAsnTer Likely pathogenic ★ same type
CEP63 p.Leu466fs Uncertain significance ★ same type
CEP63 p.Thr664fs Uncertain significance ★ same type
CEP63 c.1673+6dup Benign ★ same type
CEP63 c.790-5dup Benign ★ same type
CEP63 c.930-7dup Likely benign ★ 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-gln537fs (accessed [today's date]).

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