Is CEP131 p.Ala494Thr (c.1480G>A) pathogenic?

CEP131 p.Ala494Thr (c.1480G>A) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely benign (0.0669); Rare (popmax 0.114%, eas).

How common is CEP131 p.Ala494Thr (c.1480G>A) in the general population?

CEP131 p.Ala494Thr (c.1480G>A) is rare (popmax 0.114%, eas) (gnomAD).

What do computational predictors say about CEP131 p.Ala494Thr (c.1480G>A)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

CEP131 p.Ala494Thr

c.1480G>A · rs200083501 · VCV3142547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.03	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 -2.9
Regional constraint	o/e 1.06	unconstrained · MANE · 9,708 bp · p 0.047 · regional, not allelic
Overall
CADD	4.146	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A497T vs ClinVar A494T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% East Asian · 51/44,868 alleles

Filtering AF 0.0888% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0799%

Overall 0.00552% 89/1,612,142 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.114%	880
African / African-American	0.0107%	9,384
Admixed American	0.00334%	29,983
European (non-Finnish)	0.00229%	43,681
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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.Ala494Thr
Coding: c.1480G>A
MANE Select: NM_014984
dbSNP: rs200083501
Type: single nucleotide variant
Location: chr17:81197879 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.20

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.Ala332Ser Uncertain significance ★ ⚠ same type
CEP131 p.Ala403Val Uncertain significance ★ ⚠ same type
CEP131 p.Ala436Glu 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-ala494thr (accessed [today's date]).

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