Is ABHD1 p.Ala336Val (c.1007C>T) pathogenic?

ABHD1 p.Ala336Val (c.1007C>T) is classified Uncertain significance in ABHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.1116); Very rare (popmax 0.00659%, sas).

How common is ABHD1 p.Ala336Val (c.1007C>T) in the general population?

ABHD1 p.Ala336Val (c.1007C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ABHD1 p.Ala336Val (c.1007C>T)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

ABHD1 p.Ala336Val

c.1007C>T · VCV4636282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 6,792 bp · p 0.038 · regional, not allelic
Overall
CADD	23.7	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 0.00659% South Asian · 6/91,092 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000372% 6/1,613,966 alleles · very rare

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: ABHD1
Protein: p.Ala336Val
Coding: c.1007C>T
MANE Select: NM_032604
Type: single nucleotide variant
Location: chr2:27130533 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.75
Residue 336: the ab hydrolase-1 domain

Full ABHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD1 p.Ala154Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala172Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala326Glu Uncertain significance ★ ⚠ same type
ABHD1 p.Ala349Val Uncertain significance ★ ⚠ same type
ABHD1 p.Ala381Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala50Val Uncertain significance ★ ⚠ same type
ABHD1 p.Arg160Trp Uncertain significance ★ ⚠ same type
ABHD1 p.Arg163Cys 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/abhd1-p-ala336val (accessed [today's date]).

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