Is CEP131 p.Ala332Ser (c.994G>T) pathogenic?

CEP131 p.Ala332Ser (c.994G>T) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: ambiguous (0.3515); Ultra-rare (popmax 0.0156%, eas).

How common is CEP131 p.Ala332Ser (c.994G>T) in the general population?

CEP131 p.Ala332Ser (c.994G>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CEP131 p.Ala332Ser (c.994G>T)?

AlphaMissense predicts ambiguous (score 0.3515) — an in-silico prediction, not a clinical call.

CEP131 p.Ala332Ser

c.994G>T · VCV3831679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3515	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -7.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 7,388 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	24.9	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 0.0156% East Asian · 7/44,874 alleles

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

Overall 0.000683% 11/1,610,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
African / African-American	0.00533%	18,767

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: CEP131
Protein: p.Ala332Ser
Coding: c.994G>T
MANE Select: NM_014984
Type: single nucleotide variant
Location: chr17:81199748 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.20
Residue 332: the 'disordered' region

Full CEP131 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP131 p.Pro365Ser Uncertain significance ★★ ⚠ same type
CEP131 p.Ala1024Thr Uncertain significance ★ ⚠ same type
CEP131 p.Ala1042Ser Uncertain significance ★ ⚠ same type
CEP131 p.Ala113Pro Uncertain significance ★ ⚠ same type
CEP131 p.Ala271Pro Uncertain significance ★ ⚠ same type
CEP131 p.Ala403Val Uncertain significance ★ ⚠ same type
CEP131 p.Ala436Glu Uncertain significance ★ ⚠ same type
CEP131 p.Ala437Val Uncertain significance ★ ⚠ 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/cep131-p-ala332ser (accessed [today's date]).

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