Is CERS4 p.Glu352Ala (c.1055A>C) pathogenic?

CERS4 p.Glu352Ala (c.1055A>C) is classified Uncertain significance in CERS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.0145%, sas).

How common is CERS4 p.Glu352Ala (c.1055A>C) in the general population?

CERS4 p.Glu352Ala (c.1055A>C) is ultra-rare (popmax 0.0145%, sas) (gnomAD).

What do computational predictors say about CERS4 p.Glu352Ala (c.1055A>C)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

CERS4 p.Glu352Ala

c.1055A>C · VCV4001293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -8.25	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 0.97	GERP -0.93, phastCons 0.004
Regional constraint	o/e 1.13	unconstrained · MANE · 11 kb · p 0.0051 · regional, not allelic
Overall
CADD	10.83	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 0.0145% South Asian · 13/89,426 alleles

Filtering AF 0.00859% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00672%

Overall 0.00294% 47/1,601,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0145%	6,879
African / African-American	0.00672%	14,876
East Asian	0.00447%	22,372
European (non-Finnish)	0.00221%	45,157
Admixed American	0.00175%	57,068

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: CERS4
Protein: p.Glu352Ala
Coding: c.1055A>C
MANE Select: NM_024552
Type: single nucleotide variant
Location: chr19:8261979 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.92
Residue 352: the 'disordered' region

Full CERS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS4 p.Ala82Thr Likely benign ★★ same type
CERS4 p.Leu194= Benign ★★ same type
CERS4 p.Ala162Val Uncertain significance ★ ⚠ same type
CERS4 p.Ala373Thr Uncertain significance ★ ⚠ same type
CERS4 p.Ala46Val Uncertain significance ★ ⚠ same type
CERS4 p.Arg116Gln Uncertain significance ★ ⚠ same type
CERS4 p.Arg121His Uncertain significance ★ ⚠ same type
CERS4 p.Arg203Cys 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/cers4-p-glu352ala (accessed [today's date]).

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