Is CEP152 p.Ala995Val (c.2984C>T) pathogenic?

CEP152 p.Ala995Val (c.2984C>T) is classified Uncertain significance in CEP152 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-16). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.0391%, amr); Associated with Seckel syndrome 5.

What condition is associated with CEP152 p.Ala995Val (c.2984C>T)?

CEP152 p.Ala995Val (c.2984C>T) is associated with Seckel syndrome 5, microcephaly 9, primary, autosomal recessive (ClinVar).

How common is CEP152 p.Ala995Val (c.2984C>T) in the general population?

CEP152 p.Ala995Val (c.2984C>T) is ultra-rare (popmax 0.0391%, amr) (gnomAD).

What do computational predictors say about CEP152 p.Ala995Val (c.2984C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

CEP152 p.Ala995Val

c.2984C>T · rs146955708 · VCV1311631

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0391%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 5

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.34	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 2.1	GERP 4.4, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	23.4	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 0.0391% Admixed American · 22/56,304 alleles

Filtering AF 0.0264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.0022% 35/1,591,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0391%	2,559
African / African-American	0.00271%	36,929
South Asian	0.00115%	86,756
European (non-Finnish)	0.000855%	116,963

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.Ala995Val
Coding: c.2984C>T
MANE Select: NM_001194998
dbSNP: rs146955708
Type: single nucleotide variant
Location: chr15:48756264 (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

Seckel syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly 9, primary, autosomal recessive

Similar variants

CEP152 p.Ala995= Likely benign ★★ same residue
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

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-ala995val (accessed [today's date]).

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