Is CEP152 p.Ser894Phe (c.2681C>T) pathogenic?

CEP152 p.Ser894Phe (c.2681C>T) is classified Conflicting classifications of pathogenicity in CEP152 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1201); Low-frequency (popmax 1.3%, eas); Associated with microcephaly 9, primary, autosomal recessive.

What condition is associated with CEP152 p.Ser894Phe (c.2681C>T)?

CEP152 p.Ser894Phe (c.2681C>T) is associated with microcephaly 9, primary, autosomal recessive, Seckel syndrome 5 (ClinVar).

How common is CEP152 p.Ser894Phe (c.2681C>T) in the general population?

CEP152 p.Ser894Phe (c.2681C>T) is low-frequency (popmax 1.3%, eas) (gnomAD).

What do computational predictors say about CEP152 p.Ser894Phe (c.2681C>T)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

CEP152 p.Ser894Phe

c.2681C>T · rs145138194 · VCV158245

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 9, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 2.4, phastCons 0.08
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	13.7	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 1.3% East Asian · 583/44,868 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.0377% 609/1,613,978 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.3%	77
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.0022%	45,540
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000254%	393,295

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.Ser894Phe
Coding: c.2681C>T
MANE Select: NM_001194998
dbSNP: rs145138194
Type: single nucleotide variant
Location: chr15:48760148 (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 p.Ser894fs Pathogenic ★ 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-ser894phe (accessed [today's date]).

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