Is CEP152 p.Val12Ala (c.35T>C) pathogenic?

CEP152 p.Val12Ala (c.35T>C) is classified Conflicting classifications of pathogenicity in CEP152 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-08-12). AlphaMissense: likely benign (0.0563); Ultra-rare (popmax 0.0432%, nfe); Associated with microcephaly 9, primary, autosomal recessive.

What condition is associated with CEP152 p.Val12Ala (c.35T>C)?

CEP152 p.Val12Ala (c.35T>C) is associated with microcephaly 9, primary, autosomal recessive, Seckel syndrome 5 (ClinVar).

How common is CEP152 p.Val12Ala (c.35T>C) in the general population?

CEP152 p.Val12Ala (c.35T>C) is ultra-rare (popmax 0.0432%, nfe) (gnomAD).

What do computational predictors say about CEP152 p.Val12Ala (c.35T>C)?

AlphaMissense predicts likely benign (score 0.0563) — an in-silico prediction, not a clinical call.

CEP152 p.Val12Ala

c.35T>C · rs191061766 · VCV316432

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0563 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0432%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 9, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0563	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.63	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	GERP 4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	15.56	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 0.0432% European (non-Finnish) · 509/1,179,034 alleles

Filtering AF 0.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0388%

Overall 0.0359% 578/1,609,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0432%	2,316
Remaining individualsnot grpmax-eligible	0.0417%	2,398
Admixed American	0.0354%	2,828
Middle Eastern	0.0165%	6,048
South Asian	0.0121%	8,269
African / African-American	0.00813%	12,302
Finnishnot grpmax-eligible	0.00636%	15,720

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.Val12Ala
Coding: c.35T>C
MANE Select: NM_001194998
dbSNP: rs191061766
Type: single nucleotide variant
Location: chr15:48805615 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB
Residue 12: the 'interaction with plk4' region; the 'disordered' region

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-val12ala (accessed [today's date]).

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