Is ABHD5 p.Arg16fs (c.46_47del) pathogenic?

ABHD5 p.Arg16fs (c.4647del) is classified Pathogenic in ABHD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2001-11-01). Very rare (popmax 0.00026%, nfe); Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Arg16fs (c.46_47del)?

ABHD5 p.Arg16fs (c.46_47del) is associated with Dorfman-Chanarin disease (ClinVar).

How common is ABHD5 p.Arg16fs (c.46_47del) in the general population?

ABHD5 p.Arg16fs (c.46_47del) is very rare (popmax 0.00026%, nfe) (gnomAD).

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.Arg16fs

c.46_47del · rs387906336 · VCV5354

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00026%, nfe)

Conditions

Dorfman-Chanarin disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.052	GERP -0.68

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00026% European (non-Finnish) · 3/1,155,558 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000213% 3/1,408,460 alleles · very rare

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.Arg16fs
Coding: c.46_47del
MANE Select: NM_016006
dbSNP: rs387906336
Type: Microsatellite
Location: chr3:43691033 (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 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.Thr244fs 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-arg16fs (accessed [today's date]).

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