Is ABHD2 p.Met327Val (c.979A>G) pathogenic?

ABHD2 p.Met327Val (c.979A>G) is classified Uncertain significance in ABHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.0495%, mid).

How common is ABHD2 p.Met327Val (c.979A>G) in the general population?

ABHD2 p.Met327Val (c.979A>G) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about ABHD2 p.Met327Val (c.979A>G)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

ABHD2 p.Met327Val

c.979A>G · rs565595001 · VCV3130984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -4.33	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 9.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 79 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	17.51	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00558% 90/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Admixed American	0.0233%	4,288
Remaining individualsnot grpmax-eligible	0.0192%	5,208
African / African-American	0.00933%	10,721
European (non-Finnish)	0.00458%	21,852

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.Met327Val
Coding: c.979A>G
MANE Select: NM_152924
dbSNP: rs565595001
Type: single nucleotide variant
Location: chr15:89191132 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 327: 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-met327val (accessed [today's date]).

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