Is CERS4 p.Leu362= (c.1086A>G) pathogenic?

CERS4 p.Leu362= (c.1086A>G) is classified Likely benign in CERS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0168%, mid).

How common is CERS4 p.Leu362= (c.1086A>G) in the general population?

CERS4 p.Leu362= (c.1086A>G) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

CERS4 p.Leu362=

c.1086A>G · rs199893919 · VCV2649194

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -3.2, phastCons 0.046
Overall
CADD	2.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,950 alleles

Filtering AF 0.0019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00233% 37/1,590,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,950
Remaining individualsnot grpmax-eligible	0.00489%	20,460
European (non-Finnish)	0.00265%	37,737
Admixed American	0.00182%	54,872
Finnishnot grpmax-eligible	0.00158%	63,258

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.Leu362=
Coding: c.1086A>G
MANE Select: NM_024552
dbSNP: rs199893919
Type: single nucleotide variant
Location: chr19:8262010 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.92
Residue 362: 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-leu362 (accessed [today's date]).

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