Is CEP152 p.Ala411Pro (c.1231G>C) pathogenic?

CEP152 p.Ala411Pro (c.1231G>C) is classified Uncertain significance in CEP152 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely pathogenic (0.8618); Ultra-rare (popmax 0.0156%, eas).

How common is CEP152 p.Ala411Pro (c.1231G>C) in the general population?

CEP152 p.Ala411Pro (c.1231G>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CEP152 p.Ala411Pro (c.1231G>C)?

AlphaMissense predicts likely pathogenic (score 0.8618) — an in-silico prediction, not a clinical call.

CEP152 p.Ala411Pro

c.1231G>C · rs188488086 · VCV1374790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8618	likely pathogenic · top 4% in CEP152
REVEL	0.325	indeterminate
SaProt	LLR -11.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 0.57, phastCons 0.75
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	19.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0156% East Asian · 7/44,866 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000558% 9/1,613,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	8.48e-05%	1,179,852

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.Ala411Pro
Coding: c.1231G>C
MANE Select: NM_001194998
dbSNP: rs188488086
Type: single nucleotide variant
Location: chr15:48784063 (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

Similar variants

CEP152 p.Ala411Thr Uncertain significance ★★ ⚠ same residue
CEP152 c.1578-1G>A Likely pathogenic ★★ same type
CEP152 c.1908+1G>T Likely pathogenic ★★ same type
CEP152 c.540+1G>A Pathogenic/Likely pathogenic ★★ same type
CEP152 c.88-2A>G Likely pathogenic ★★ same type
CEP152 c.972+2T>A Likely pathogenic ★★ same type
CEP152 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
CEP152 p.Arg1309Ter Pathogenic/Likely pathogenic ★★ 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/cep152-p-ala411pro (accessed [today's date]).

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