Is CEP131 p.Ala271Pro (c.811G>C) pathogenic?

CEP131 p.Ala271Pro (c.811G>C) is classified Uncertain significance in CEP131 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely pathogenic (0.9474); Very rare (popmax 0.00105%, nfe).

How common is CEP131 p.Ala271Pro (c.811G>C) in the general population?

CEP131 p.Ala271Pro (c.811G>C) is very rare (popmax 0.00105%, nfe) (gnomAD).

What do computational predictors say about CEP131 p.Ala271Pro (c.811G>C)?

AlphaMissense predicts likely pathogenic (score 0.9474) — an in-silico prediction, not a clinical call.

CEP131 p.Ala271Pro

c.811G>C · rs768192457 · VCV2480282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00105%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9474	likely pathogenic · top 1% in CEP131
REVEL	0.477	indeterminate
SaProt	LLR -14.90	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 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 7,388 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	27.7	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 0.00105% European (non-Finnish) · 12/1,147,470 alleles

Filtering AF 0.000558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00044%

Overall 0.000858% 12/1,398,442 alleles · very rare

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.Ala271Pro
Coding: c.811G>C
MANE Select: NM_014984
dbSNP: rs768192457
Type: single nucleotide variant
Location: chr17:81200424 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.20
Residue 271: the iq domain

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.Ala332Ser 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-ala271pro (accessed [today's date]).

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