Is ABHD6 p.Val103Met (c.307G>A) pathogenic?

ABHD6 p.Val103Met (c.307G>A) is classified Uncertain significance in ABHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.4068); Very rare (popmax 0.00223%, eas).

How common is ABHD6 p.Val103Met (c.307G>A) in the general population?

ABHD6 p.Val103Met (c.307G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABHD6 p.Val103Met (c.307G>A)?

AlphaMissense predicts ambiguous (score 0.4068) — an in-silico prediction, not a clinical call.

ABHD6 p.Val103Met

c.307G>A · VCV4636340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4068	ambiguous
REVEL	0.474	indeterminate
SaProt	LLR -5.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.038 · regional, not allelic
Overall
CADD	31.0	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 0.00223% East Asian · 1/44,876 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00157% 23/1,461,628 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
European (non-Finnish)	0.00186%	53,631

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.Val103Met
Coding: c.307G>A
MANE Select: NM_001320126
Type: single nucleotide variant
Location: chr3:58269351 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 103: a β-strand; the ab hydrolase-1 domain

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-val103met (accessed [today's date]).

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