Is ABHD1 p.Arg285Cys (c.853C>T) pathogenic?

ABHD1 p.Arg285Cys (c.853C>T) is classified Uncertain significance in ABHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-29). AlphaMissense: likely benign (0.0903); Very rare (popmax 0.00439%, sas).

How common is ABHD1 p.Arg285Cys (c.853C>T) in the general population?

ABHD1 p.Arg285Cys (c.853C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ABHD1 p.Arg285Cys (c.853C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

ABHD1 p.Arg285Cys

c.853C>T · VCV3421913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.1, phastCons 0.99
Regional constraint	o/e 1.09	unconstrained · MANE · 6,792 bp · p 0.038 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,092 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00211% 34/1,614,010 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
Admixed American	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.0022%	45,386

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: ABHD1
Protein: p.Arg285Cys
Coding: c.853C>T
MANE Select: NM_032604
Type: single nucleotide variant
Location: chr2:27130263 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.75
Residue 285: the ab hydrolase-1 domain

Full ABHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD1 p.Arg285His Uncertain significance ★ ⚠ same residue
ABHD1 p.Ala154Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala172Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala326Glu Uncertain significance ★ ⚠ same type
ABHD1 p.Ala336Val Uncertain significance ★ ⚠ same type
ABHD1 p.Ala349Val Uncertain significance ★ ⚠ same type
ABHD1 p.Ala381Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala50Val Uncertain significance ★ ⚠ same type

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/abhd1-p-arg285cys (accessed [today's date]).

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