Is CERS2 p.Leu289Val (c.865C>G) pathogenic?

CERS2 p.Leu289Val (c.865C>G) is classified Likely benign in CERS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0621); Absent from gnomAD v4.1.

How common is CERS2 p.Leu289Val (c.865C>G) in the general population?

CERS2 p.Leu289Val (c.865C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS2 p.Leu289Val (c.865C>G)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

CERS2 p.Leu289Val

c.865C>G · VCV4226663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.14	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 0.005	GERP -3.5
Regional constraint	o/e 0.80	unconstrained · MANE · 670 bp · p 0.015 · regional, not allelic
Overall
CADD	2.219	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: CERS2
Protein: p.Leu289Val
Coding: c.865C>G
MANE Select: NM_022075
Type: single nucleotide variant
Location: chr1:150966613 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 87.31
Residue 289: the tlc domain

Full CERS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS2 p.Ala152= Benign ★★ same type
CERS2 p.Ser199= Benign ★★ same type
CERS2 p.Tyr254= Benign ★★ same type
CERS2 p.Ala23Ser Uncertain significance ★ ⚠ same type
CERS2 p.Ala23Val Uncertain significance ★ ⚠ same type
CERS2 p.Ala34Thr Uncertain significance ★ same type
CERS2 p.Ala46Gly Uncertain significance ★ ⚠ same type
CERS2 p.Arg105Leu 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/cers2-p-leu289val (accessed [today's date]).

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