Is ABHD5 p.Gln130Pro (c.389A>C) pathogenic?

ABHD5 p.Gln130Pro (c.389A>C) is classified Pathogenic in ABHD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-07-16). AlphaMissense: likely pathogenic (0.9453); Absent from gnomAD v4.1; Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Gln130Pro (c.389A>C)?

ABHD5 p.Gln130Pro (c.389A>C) is associated with Dorfman-Chanarin disease (ClinVar).

How common is ABHD5 p.Gln130Pro (c.389A>C) in the general population?

ABHD5 p.Gln130Pro (c.389A>C) is absent from gnomAD v4.1 (gnomAD).

How is Neutral lipid storage disease with ichthyosis inherited?

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

What do computational predictors say about ABHD5 p.Gln130Pro (c.389A>C)?

AlphaMissense predicts likely pathogenic (score 0.9453) — an in-silico prediction, not a clinical call.

ABHD5 p.Gln130Pro

c.389A>C · rs28939077 · VCV5350

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9453 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dorfman-Chanarin disease

Computational evidence

Protein change
AlphaMissense	0.9453	likely pathogenic ✓ concordant with ClinVar
REVEL	0.662	pathogenic-leaning
SaProt	LLR -17.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABHD5
Protein: p.Gln130Pro
Coding: c.389A>C
MANE Select: NM_016006
dbSNP: rs28939077
Type: single nucleotide variant
Location: chr3:43702470 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62
Residue 130: a UniProt-annotated variant site (in cds; loss of pnpla2-dependent triacylclycerol hydrolysis but no effect on lpa acyltransferase activity); the ab hydrolase-1 domain

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 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
ABHD5 p.Leu214Ile 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-gln130pro (accessed [today's date]).

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