Is ABHD6 p.Met310Thr (c.929T>C) pathogenic?

ABHD6 p.Met310Thr (c.929T>C) is classified Uncertain significance in ABHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.4737); Ultra-rare (popmax 0.0387%, afr).

How common is ABHD6 p.Met310Thr (c.929T>C) in the general population?

ABHD6 p.Met310Thr (c.929T>C) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

What do computational predictors say about ABHD6 p.Met310Thr (c.929T>C)?

AlphaMissense predicts ambiguous (score 0.4737) — an in-silico prediction, not a clinical call.

ABHD6 p.Met310Thr

c.929T>C · VCV4636341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4737 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4737	ambiguous
REVEL	0.23	benign-leaning
SaProt	LLR -6.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.038 · regional, not allelic
Overall
CADD	24.0	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 0.0387% African / African-American · 29/74,932 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00223% 36/1,614,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,584
Remaining individualsnot grpmax-eligible	0.008%	12,496
Admixed American	0.00167%	60,010
European (non-Finnish)	8.47e-05%	1,180,040

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.Met310Thr
Coding: c.929T>C
MANE Select: NM_001320126
Type: single nucleotide variant
Location: chr3:58293680 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 310: the ab hydrolase-1 domain; an α-helix

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-met310thr (accessed [today's date]).

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