Is CERS5 p.Ile233Leu (c.697A>C) pathogenic?

CERS5 p.Ile233Leu (c.697A>C) is classified Uncertain significance in CERS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0937); Absent from gnomAD v4.1.

How common is CERS5 p.Ile233Leu (c.697A>C) in the general population?

CERS5 p.Ile233Leu (c.697A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS5 p.Ile233Leu (c.697A>C)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

CERS5 p.Ile233Leu

c.697A>C · rs367900841 · VCV3143180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -8.15	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 1.5	GERP -3.7, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 33 kb · p 0.004 · regional, not allelic
Overall
CADD	18.76	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: CERS5
Protein: p.Ile233Leu
Coding: c.697A>C
MANE Select: NM_147190
dbSNP: rs367900841
Type: single nucleotide variant
Location: chr12:50136009 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.91
Residue 233: the tlc domain

Full CERS5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS5 p.Ala278Val Uncertain significance ★ ⚠ same type
CERS5 p.Ala2Thr Uncertain significance ★ ⚠ same type
CERS5 p.Ala338Ser Uncertain significance ★ ⚠ same type
CERS5 p.Ala377Thr Uncertain significance ★ ⚠ same type
CERS5 p.Arg127His Uncertain significance ★ ⚠ same type
CERS5 p.Arg238Gln Uncertain significance ★ ⚠ same type
CERS5 p.Arg267Gln Uncertain significance ★ ⚠ same type
CERS5 p.Arg284Gln 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/cers5-p-ile233leu (accessed [today's date]).

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