Is ABHD6 p.Ser252Arg (c.756T>A) pathogenic?

ABHD6 p.Ser252Arg (c.756T>A) is classified Uncertain significance in ABHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.268); Absent from gnomAD v4.1.

How common is ABHD6 p.Ser252Arg (c.756T>A) in the general population?

ABHD6 p.Ser252Arg (c.756T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD6 p.Ser252Arg (c.756T>A)?

AlphaMissense predicts likely benign (score 0.268) — an in-silico prediction, not a clinical call.

ABHD6 p.Ser252Arg

c.756T>A · VCV3789286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.268 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.268	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -13.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.31	GERP -1.8
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.038 · regional, not allelic
Overall
CADD	14.74	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABHD6
Protein: p.Ser252Arg
Coding: c.756T>A
MANE Select: NM_001320126
Type: single nucleotide variant
Location: chr3:58285372 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 252: 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-ser252arg (accessed [today's date]).

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