Is CES2 p.Met488Lys (c.1463T>A) pathogenic?

CES2 p.Met488Lys (c.1463T>A) is classified Uncertain significance in CES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: ambiguous (0.4302); Absent from gnomAD v4.1.

How common is CES2 p.Met488Lys (c.1463T>A) in the general population?

CES2 p.Met488Lys (c.1463T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CES2 p.Met488Lys (c.1463T>A)?

AlphaMissense predicts ambiguous (score 0.4302) — an in-silico prediction, not a clinical call.

CES2 p.Met488Lys

c.1463T>A · rs757178123 · VCV2612451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4302 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4302	ambiguous
REVEL	0.743	pathogenic-leaning
SaProt	LLR -15.30	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.9, phastCons 1
Overall
CADD	24.4	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: CES2
Protein: p.Met488Lys
Coding: c.1463T>A
MANE Select: NM_001025195 · reported on NM_001365405
dbSNP: rs757178123
Type: single nucleotide variant
Location: chr16:66943341 (GRCh38)
Structure: AlphaFold pLDDT 93.27 · 21 PDB
Residue 488: an α-helix

Full CES2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CES1 p.Val166Met Uncertain significance ★★ ⚠ same type
CES2 p.Glu366= Benign ★★ same type
CES1 p.Ala126Asp Uncertain significance ★ ⚠ same type
CES1 p.Ala126Val Uncertain significance ★ ⚠ same type
CES1 p.Ala149Glu Uncertain significance ★ ⚠ same type
CES1 p.Ala160Thr Uncertain significance ★ ⚠ same type
CES1 p.Ala197Asp Uncertain significance ★ ⚠ same type
CES1 p.Ala338Gly 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/ces2-p-met488lys (accessed [today's date]).

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