Is ABHD5 p.Arg184Ter (c.550C>T) pathogenic?

ABHD5 p.Arg184Ter (c.550C>T) is classified Pathogenic in ABHD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00333%, amr); Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Arg184Ter (c.550C>T)?

ABHD5 p.Arg184Ter (c.550C>T) is associated with Dorfman-Chanarin disease (ClinVar).

How common is ABHD5 p.Arg184Ter (c.550C>T) in the general population?

ABHD5 p.Arg184Ter (c.550C>T) is very rare (popmax 0.00333%, amr) (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.Arg184Ter

c.550C>T · rs138876970 · VCV973467

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Dorfman-Chanarin disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
African / African-American	0.00267%	37,460
South Asian	0.0022%	45,545
Finnishnot grpmax-eligible	0.00156%	64,026

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.Arg184Ter
Coding: c.550C>T
MANE Select: NM_016006
dbSNP: rs138876970
Type: single nucleotide variant
Location: chr3:43711752 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62
Residue 184: 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 p.Arg184Gln Uncertain significance ★ ⚠ same residue
ABHD5 p.Arg184= Likely benign ★ same residue
ABHD5 c.507-1G>A 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-arg184ter (accessed [today's date]).

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