Is CEP152 p.Glu754= (c.2262G>A) pathogenic?

CEP152 p.Glu754= (c.2262G>A) is classified Conflicting classifications of pathogenicity in CEP152 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-29). Rare (popmax 0.273%, nfe); Associated with microcephaly 9, primary, autosomal recessive.

What condition is associated with CEP152 p.Glu754= (c.2262G>A)?

CEP152 p.Glu754= (c.2262G>A) is associated with microcephaly 9, primary, autosomal recessive, Seckel syndrome 5 (ClinVar).

How common is CEP152 p.Glu754= (c.2262G>A) in the general population?

CEP152 p.Glu754= (c.2262G>A) is rare (popmax 0.273%, nfe) (gnomAD).

CEP152 p.Glu754=

c.2262G>A · rs149176738 · VCV158242

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.273%, nfe)

Conditions

microcephaly 9, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	phastCons 1
Overall
CADD	2.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.273% European (non-Finnish) · 3,220/1,179,982 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.262%

Overall 0.235% 3,788/1,613,152 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.361%	277
European (non-Finnish)grpmax	0.273%	366
Remaining individualsnot grpmax-eligible	0.2%	500
Middle Eastern	0.198%	505
South Asian	0.115%	867
Admixed American	0.105%	953
African / African-American	0.0346%	2,886
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
East Asian	0.00223%	44,860

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CEP152
Protein: p.Glu754=
Coding: c.2262G>A
MANE Select: NM_001194998
dbSNP: rs149176738
Type: single nucleotide variant
Location: chr15:48767078 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB

Full CEP152 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 9, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Seckel syndrome 5

Similar variants

CEP152 c.1908+1G>T Likely pathogenic ★★ same condition
CEP152 c.540+1G>A Pathogenic/Likely pathogenic ★★ same condition
CEP152 c.972+2T>A Likely pathogenic ★★ same condition
CEP152 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg1309Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg267Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg987Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Gln265Pro Pathogenic/Likely pathogenic ★★ same condition

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/cep152-p-glu754 (accessed [today's date]).

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