Is CER1 p.Lys89Met (c.266A>T) pathogenic?

CER1 p.Lys89Met (c.266A>T) is classified Uncertain significance in CER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: likely benign (0.1712); Absent from gnomAD v4.1.

How common is CER1 p.Lys89Met (c.266A>T) in the general population?

CER1 p.Lys89Met (c.266A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CER1 p.Lys89Met (c.266A>T)?

AlphaMissense predicts likely benign (score 0.1712) — an in-silico prediction, not a clinical call.

CER1 p.Lys89Met

c.266A>T · VCV3832136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1712	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.73	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 4.9	phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 2,579 bp · p 8.8e-09 · regional, not allelic
Overall
CADD	23.1	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

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: CER1
Protein: p.Lys89Met
Coding: c.266A>T
Type: single nucleotide variant
Location: chr9:14722407 (GRCh38)

Full CER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CER1 p.Ala198Val Uncertain significance ★ ⚠ same type
CER1 p.Ala199Gly Uncertain significance ★ ⚠ same type
CER1 p.Ala199Val Uncertain significance ★ ⚠ same type
CER1 p.Ala59Thr Uncertain significance ★ ⚠ same type
CER1 p.Arg24Cys Uncertain significance ★ ⚠ same type
CER1 p.Arg24His Uncertain significance ★ ⚠ same type
CER1 p.Arg85Lys Uncertain significance ★ ⚠ same type
CER1 p.Arg92Thr 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/cer1-p-lys89met (accessed [today's date]).

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