Is CERS4 p.Glu7Lys (c.19G>A) pathogenic?

CERS4 p.Glu7Lys (c.19G>A) is classified Uncertain significance in CERS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0844); Ultra-rare (popmax 0.0381%, sas).

How common is CERS4 p.Glu7Lys (c.19G>A) in the general population?

CERS4 p.Glu7Lys (c.19G>A) is ultra-rare (popmax 0.0381%, sas) (gnomAD).

What do computational predictors say about CERS4 p.Glu7Lys (c.19G>A)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

CERS4 p.Glu7Lys

c.19G>A · VCV4226673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0381%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.45	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 0.59, phastCons 0.05
Regional constraint	o/e 1.13	unconstrained · MANE · 11 kb · p 0.0051 · regional, not allelic
Overall
CADD	19.43	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 0.0381% South Asian · 34/89,210 alleles

Filtering AF 0.028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0245%

Overall 0.00312% 50/1,604,546 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0381%	2,624
Remaining individualsnot grpmax-eligible	0.00483%	20,719
Admixed American	0.00343%	29,133
East Asian	0.00227%	44,018
European (non-Finnish)	0.00085%	117,606

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.Glu7Lys
Coding: c.19G>A
MANE Select: NM_024552
Type: single nucleotide variant
Location: chr19:8251095 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.92

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-glu7lys (accessed [today's date]).

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