Is CEP126 p.Met288Ile (c.864G>T) pathogenic?

CEP126 p.Met288Ile (c.864G>T) is classified Uncertain significance in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1146); Very rare (popmax 0.00669%, eas).

How common is CEP126 p.Met288Ile (c.864G>T) in the general population?

CEP126 p.Met288Ile (c.864G>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CEP126 p.Met288Ile (c.864G>T)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

CEP126 p.Met288Ile

c.864G>T · VCV4225842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.61	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 -0.24	GERP -4, phastCons 0.005
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	0.147	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,836 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000205% 3/1,460,962 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: CEP126
Protein: p.Met288Ile
Coding: c.864G>T
MANE Select: NM_020802
Type: single nucleotide variant
Location: chr11:101961899 (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-met288ile (accessed [today's date]).

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