Is CERS3 p.Arg92Lys (c.275G>A) pathogenic?

CERS3 p.Arg92Lys (c.275G>A) is classified Uncertain significance in CERS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with CERS3 p.Arg92Lys (c.275G>A)?

CERS3 p.Arg92Lys (c.275G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CERS3 p.Arg92Lys (c.275G>A) in the general population?

CERS3 p.Arg92Lys (c.275G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CERS3 p.Arg92Lys (c.275G>A)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

CERS3 p.Arg92Lys

c.275G>A · VCV4614022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -4.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP 0.36, phastCons 0.026
Regional constraint	o/e 1.02	unconstrained · MANE · 99 kb · p 0.65 · regional, not allelic
Overall
CADD	10.39	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 0.00334% Admixed American · 2/59,802 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000138% 2/1,451,798 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: CERS3
Protein: p.Arg92Lys
Coding: c.275G>A
MANE Select: NM_001378789
Type: single nucleotide variant
Location: chr15:100490830 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.52
Residue 92: the 'homeobox-like' region

Full CERS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CERS3 p.Arg275Cys Uncertain significance ★★ ⚠ same condition
CERS3 p.Ser177Phe Uncertain significance ★★ ⚠ same condition
CERS3 p.Val60Ile Likely benign ★★ same condition
CERS3 p.Ala151Val Uncertain significance ★ ⚠ same condition
CERS3 p.Arg111Gly Uncertain significance ★ ⚠ same condition
CERS3 p.Arg128Met Uncertain significance ★ ⚠ same condition
CERS3 p.Arg339Lys Uncertain significance ★ ⚠ same condition
CERS3 p.Arg54Cys Uncertain significance ★ ⚠ same condition

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/cers3-p-arg92lys (accessed [today's date]).

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