Is ABHD5 p.Ser115Arg (c.345T>A) pathogenic?

ABHD5 p.Ser115Arg (c.345T>A) is classified Likely pathogenic in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Ser115Arg (c.345T>A)?

ABHD5 p.Ser115Arg (c.345T>A) is associated with Dorfman-Chanarin disease (ClinVar).

How common is ABHD5 p.Ser115Arg (c.345T>A) in the general population?

ABHD5 p.Ser115Arg (c.345T>A) 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.Ser115Arg (c.345T>A)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

ABHD5 p.Ser115Arg

c.345T>A · VCV3340145

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · 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	0.9975	likely pathogenic ✓ concordant with ClinVar · top 1% in ABHD5
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -15.12	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 0.61	GERP -4.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	23.7	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.Ser115Arg
Coding: c.345T>A
MANE Select: NM_016006
Type: single nucleotide variant
Location: chr3:43702426 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62
Residue 115: the ab hydrolase-1 domain; a UniProt-annotated variant site (in cds)

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.Ser115= Uncertain significance ★ same residue
ABHD5 p.Ser115Asn Uncertain significance ★ ⚠ 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

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-ser115arg (accessed [today's date]).

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