Is ABHD1 p.Arg191His (c.572G>A) pathogenic?

ABHD1 p.Arg191His (c.572G>A) is classified Uncertain significance in ABHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0691); Ultra-rare (popmax 0.03%, amr).

How common is ABHD1 p.Arg191His (c.572G>A) in the general population?

ABHD1 p.Arg191His (c.572G>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about ABHD1 p.Arg191His (c.572G>A)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

ABHD1 p.Arg191His

c.572G>A · rs144288127 · VCV3130041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.64	GERP -4.7
Regional constraint	o/e 1.09	unconstrained · MANE · 6,792 bp · p 0.038 · regional, not allelic
Overall
CADD	4.005	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 0.03% Admixed American · 18/59,998 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00762% 123/1,613,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
European (non-Finnish)	0.00822%	12,166
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.00329%	30,365
African / African-American	0.00267%	37,456

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.Arg191His
Coding: c.572G>A
MANE Select: NM_032604
dbSNP: rs144288127
Type: single nucleotide variant
Location: chr2:27129581 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.75
Residue 191: the ab hydrolase-1 domain

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

Similar variants

ABHD1 p.Arg191Cys 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-arg191his (accessed [today's date]).

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