Is ABHD5 p.Glu4= (c.12G>A) pathogenic?

ABHD5 p.Glu4= (c.12G>A) is classified Benign in ABHD5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 9.04%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Glu4= (c.12G>A)?

ABHD5 p.Glu4= (c.12G>A) is associated with Dorfman-Chanarin disease (ClinVar).

How is Neutral lipid storage disease with ichthyosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABHD5 p.Glu4=

Q: How common is ABHD5 p.Glu4= (c.12G>A) in the general population?

ABHD5 p.Glu4= (c.12G>A) is common (popmax 9.04%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.12G>A · rs141365045 · VCV345214

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 9.04%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Dorfman-Chanarin disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP -1.8, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.04% South Asian · 7,826/86,592 alleles

Filtering AF 8.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.8%

Overall 2.76% 43,400/1,569,968 alleles · common exomes 39,971/1,417,930 · genomes 3,429/152,038 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	9.04%	11
Middle Eastern	4.43%	23
Remaining individualsnot grpmax-eligible	3.11%	32
Ashkenazi Jewishnot grpmax-eligible	3.07%	33
East Asian	2.97%	34
Admixed American	2.84%	35
European (non-Finnish)	2.45%	41
African / African-American	1.28%	78
Finnishnot grpmax-eligible	0.706%	142

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: ABHD5
Protein: p.Glu4=
Coding: c.12G>A
MANE Select: NM_016006
dbSNP: rs141365045
Type: single nucleotide variant
Location: chr3:43691004 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62

Full ABHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dorfman-Chanarin disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neutral lipid storage disease with ichthyosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ABHD5 p.Glu4Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
ABHD5 c.507-1G>A Pathogenic ★★ same condition
ABHD5 p.Arg184Ter Pathogenic ★★ same condition
ABHD5 p.Arg234Ter Pathogenic ★★ same condition
ABHD5 p.Arg280Ter Pathogenic/Likely pathogenic ★★ same condition
ABHD5 p.Glu336Ter Pathogenic/Likely pathogenic ★★ same condition
ABHD5 p.Cys140Gly Uncertain significance ★★ ⚠ same condition
ABHD5 p.Glu15Lys Uncertain significance ★★ ⚠ same condition

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/abhd5-p-glu4 (accessed [today's date]).

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