Is ABHD5 p.Met239Val (c.715A>G) pathogenic?

ABHD5 p.Met239Val (c.715A>G) is classified Uncertain significance in ABHD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-06). AlphaMissense: likely benign (0.0802); Very rare (popmax 0.00667%, amr).

How common is ABHD5 p.Met239Val (c.715A>G) in the general population?

ABHD5 p.Met239Val (c.715A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ABHD5 p.Met239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

ABHD5 p.Met239Val

c.715A>G · rs189325485 · VCV392179

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -2.24	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 7.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	17.56	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 0.00667% Admixed American · 4/59,986 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00186% 30/1,613,246 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
Finnishnot grpmax-eligible	0.00313%	31,935
African / African-American	0.00267%	37,471
European (non-Finnish)	0.00178%	56,170
South Asian	0.0011%	91,050

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.Met239Val
Coding: c.715A>G
MANE Select: NM_016006
dbSNP: rs189325485
Type: single nucleotide variant
Location: chr3:43715000 (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

Similar variants

ABHD5 c.133+1G>A Likely pathogenic ★★ same type
ABHD5 c.507-1G>A Pathogenic ★★ same type
ABHD5 p.Arg184Ter Pathogenic ★★ same type
ABHD5 p.Arg234Ter Pathogenic ★★ same type
ABHD5 p.Arg280Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Glu336Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Arg56His Uncertain significance ★★ ⚠ same type
ABHD5 p.Asp12Asn 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/abhd5-p-met239val (accessed [today's date]).

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