Is CERS3 p.Arg370Ser (c.1110G>T) pathogenic?

CERS3 p.Arg370Ser (c.1110G>T) is classified Conflicting classifications of pathogenicity in CERS3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1205); Rare (popmax 0.105%, eas).

How common is CERS3 p.Arg370Ser (c.1110G>T) in the general population?

CERS3 p.Arg370Ser (c.1110G>T) is rare (popmax 0.105%, eas) (gnomAD).

What do computational predictors say about CERS3 p.Arg370Ser (c.1110G>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

CERS3 p.Arg370Ser

c.1110G>T · VCV4749456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -4.56	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 -0.55	GERP 0.84
Regional constraint	o/e 1.02	unconstrained · MANE · 99 kb · p 0.65 · regional, not allelic
Overall
CADD	5.001	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 0.105% East Asian · 47/44,874 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.00341% 55/1,614,168 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	955
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asian	0.00329%	30,361

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.Arg370Ser
Coding: c.1110G>T
MANE Select: NM_001378789
Type: single nucleotide variant
Location: chr15:100402755 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.52
Residue 370: a UniProt-annotated variant site (in)

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

Similar variants

CERS3 p.Arg370Gly Benign ★★ same residue
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

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-arg370ser (accessed [today's date]).

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