Is CEP126 p.Val431Met (c.1291G>A) pathogenic?

CEP126 p.Val431Met (c.1291G>A) is classified Likely benign in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0849); Absent from gnomAD v4.1.

How common is CEP126 p.Val431Met (c.1291G>A) in the general population?

CEP126 p.Val431Met (c.1291G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP126 p.Val431Met (c.1291G>A)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

CEP126 p.Val431Met

c.1291G>A · VCV4000568

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.06	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 3	GERP -2.2, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	6.311	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP126
Protein: p.Val431Met
Coding: c.1291G>A
MANE Select: NM_020802
Type: single nucleotide variant
Location: chr11:101962326 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.44

Full CEP126 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP126 p.Gln146Glu Benign ★★ same type
CEP126 p.His308Leu Benign ★★ same type
CEP126 p.Leu226= Benign ★★ same type
CEP126 p.Met1021Thr Benign ★★ same type
CEP126 p.Pro710Ser Benign ★★ same type
CEP126 p.Ser372Pro Benign ★★ same type
CEP126 p.Ala1028Thr Uncertain significance ★ ⚠ same type
CEP126 p.Ala460Val 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/cep126-p-val431met (accessed [today's date]).

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