Is CERS3 p.Trp15Arg (c.43T>A) pathogenic?

CERS3 p.Trp15Arg (c.43T>A) is classified Pathogenic in CERS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely pathogenic (0.9857); Very rare (popmax 0.000339%, nfe).

How common is CERS3 p.Trp15Arg (c.43T>A) in the general population?

CERS3 p.Trp15Arg (c.43T>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CERS3 p.Trp15Arg (c.43T>A)?

AlphaMissense predicts likely pathogenic (score 0.9857) — an in-silico prediction, not a clinical call.

CERS3 p.Trp15Arg

c.43T>A · rs762679102 · VCV1451147

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9857	likely pathogenic ✓ concordant with ClinVar · top 1% in CERS3
REVEL	0.742	pathogenic-leaning
SaProt	LLR -14.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 99 kb · p 0.65 · regional, not allelic
Overall
CADD	28.2	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,994 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,834 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.Trp15Arg
Coding: c.43T>A
MANE Select: NM_001378789
dbSNP: rs762679102
Type: single nucleotide variant
Location: chr15:100501807 (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

Similar variants

CERS3 c.466-1G>T Likely pathogenic ★★ same type
CERS3 p.Arg75Ter Likely pathogenic ★★ same type
CERS3 p.Arg275Cys Uncertain significance ★★ ⚠ same type
CERS3 p.Ser177Phe Uncertain significance ★★ ⚠ same type
CERS3 c.174-81G>A Benign ★★ same type
CERS3 c.407+74C>T Benign ★★ same type
CERS3 c.465+65A>T Benign ★★ same type
CERS3 c.466-110G>T Benign ★★ 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/cers3-p-trp15arg (accessed [today's date]).

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