Is ABHD6 p.Met149Val (c.445A>G) pathogenic?

ABHD6 p.Met149Val (c.445A>G) is classified Uncertain significance in ABHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: ambiguous (0.5529); Ultra-rare (popmax 0.0164%, mid).

How common is ABHD6 p.Met149Val (c.445A>G) in the general population?

ABHD6 p.Met149Val (c.445A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ABHD6 p.Met149Val (c.445A>G)?

AlphaMissense predicts ambiguous (score 0.5529) — an in-silico prediction, not a clinical call.

ABHD6 p.Met149Val

c.445A>G · VCV3323517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5529	ambiguous
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -9.18	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.038 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,612,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0016%	62,434
European (non-Finnish)	0.00017%	589,849

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: ABHD6
Protein: p.Met149Val
Coding: c.445A>G
MANE Select: NM_001320126
Type: single nucleotide variant
Location: chr3:58270986 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 149: an α-helix; the ab hydrolase-1 domain; a binding site

Full ABHD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD6 p.Ala12Val Uncertain significance ★ ⚠ same type
ABHD6 p.Ala158Asp Uncertain significance ★ ⚠ same type
ABHD6 p.Ala196Thr Uncertain significance ★ ⚠ same type
ABHD6 p.Ala82Asp Uncertain significance ★ ⚠ same type
ABHD6 p.Arg221Cys Uncertain significance ★ ⚠ same type
ABHD6 p.Arg236His Uncertain significance ★ ⚠ same type
ABHD6 p.Arg244Gln Uncertain significance ★ ⚠ same type
ABHD6 p.Arg51His 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/abhd6-p-met149val (accessed [today's date]).

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