Is ABHD2 p.Arg328Gln (c.983G>A) pathogenic?

ABHD2 p.Arg328Gln (c.983G>A) is classified Uncertain significance in ABHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.1029); Very rare (popmax 0.00439%, sas).

How common is ABHD2 p.Arg328Gln (c.983G>A) in the general population?

ABHD2 p.Arg328Gln (c.983G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ABHD2 p.Arg328Gln (c.983G>A)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

ABHD2 p.Arg328Gln

c.983G>A · rs751133771 · VCV2223170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 79 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	24.0	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 · 4/91,066 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.0031% 50/1,613,778 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.011%	9,130
South Asiangrpmax	0.00439%	22,766
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00314%	31,892

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABHD2
Protein: p.Arg328Gln
Coding: c.983G>A
MANE Select: NM_152924
dbSNP: rs751133771
Type: single nucleotide variant
Location: chr15:89191136 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 328: the ab hydrolase-1 domain

Full ABHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD2 p.His312= Benign ★★ same type
ABHD2 p.Tyr400= Benign ★★ same type
ABHD2 p.Val420= Benign ★★ same type
ABHD2 p.Ala222Gly Uncertain significance ★ ⚠ same type
ABHD2 p.Ala274Thr Uncertain significance ★ ⚠ same type
ABHD2 p.Arg175Cys Uncertain significance ★ ⚠ same type
ABHD2 p.Arg254Gln Uncertain significance ★ ⚠ same type
ABHD2 p.Arg293Gln 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/abhd2-p-arg328gln (accessed [today's date]).

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