Is ABHD5 p.Arg312Ter (c.934C>T) pathogenic?

ABHD5 p.Arg312Ter (c.934C>T) is classified Pathogenic in ABHD5 (ClinVar, Single submitter, 1 submitter). Ultra-rare (popmax 0.0164%, mid); Associated with Dorfman-Chanarin disease.

What condition is associated with ABHD5 p.Arg312Ter (c.934C>T)?

ABHD5 p.Arg312Ter (c.934C>T) is associated with Dorfman-Chanarin disease (ClinVar).

How common is ABHD5 p.Arg312Ter (c.934C>T) in the general population?

ABHD5 p.Arg312Ter (c.934C>T) is ultra-rare (popmax 0.0164%, mid) (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.Arg312Ter

c.934C>T · rs761087968 · VCV619125

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Dorfman-Chanarin disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (6 of 7, 26 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
REVEL	0.498	indeterminate
Splicing
SpliceAI	Δ0.29	donor loss · deltas
Pangolin	Δ0.45	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 0.98
Overall
CADD	38.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00124% 20/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00667%	14,985
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.0011%	90,773

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.Arg312Ter
Coding: c.934C>T
MANE Select: NM_016006
dbSNP: rs761087968
Type: single nucleotide variant
Location: chr3:43717831 (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.Arg312= Likely benign ★ 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-arg312ter (accessed [today's date]).

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