Is CERS3 p.Arg339Lys (c.1016G>A) pathogenic?

CERS3 p.Arg339Lys (c.1016G>A) is classified Uncertain significance in CERS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.7262); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CERS3 p.Arg339Lys (c.1016G>A)?

CERS3 p.Arg339Lys (c.1016G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CERS3 p.Arg339Lys (c.1016G>A) in the general population?

CERS3 p.Arg339Lys (c.1016G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS3 p.Arg339Lys (c.1016G>A)?

AlphaMissense predicts likely pathogenic (score 0.7262) — an in-silico prediction, not a clinical call.

CERS3 p.Arg339Lys

c.1016G>A · VCV4614027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7262 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7262	likely pathogenic
REVEL	0.286	benign-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 99 kb · p 0.65 · regional, not allelic
Overall
CADD	23.0	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: CERS3
Protein: p.Arg339Lys
Coding: c.1016G>A
MANE Select: NM_001378789
Type: single nucleotide variant
Location: chr15:100402849 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.52

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.Arg339= Likely benign ★ same residue
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.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-arg339lys (accessed [today's date]).

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