Is ABHD12 p.Arg181Ser (c.543A>T) pathogenic?

ABHD12 p.Arg181Ser (c.543A>T) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABHD12 p.Arg181Ser (c.543A>T)?

ABHD12 p.Arg181Ser (c.543A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD12 p.Arg181Ser (c.543A>T) in the general population?

ABHD12 p.Arg181Ser (c.543A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD12 p.Arg181Ser (c.543A>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

ABHD12 p.Arg181Ser

c.543A>T · VCV3992691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 1% in ABHD12
REVEL	0.335	indeterminate
SaProt	LLR -15.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ABHD12
Protein: p.Arg181Ser
Coding: c.543A>T
MANE Select: NM_001042472
Type: single nucleotide variant
Location: chr20:25317078 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 181: a UniProt-annotated variant site (in pharc); a UniProt-annotated variant site (in pharc; uncertain significance)

Full ABHD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABHD12 p.Ala152Thr Uncertain significance ★★ ⚠ same condition
ABHD12 p.Ala29Thr Uncertain significance ★★ ⚠ same condition
ABHD12 p.Ala330Thr Uncertain significance ★★ ⚠ same condition
ABHD12 p.Ala348Val Uncertain significance ★★ ⚠ same condition
ABHD12 p.Ala61Glu Uncertain significance ★★ ⚠ same condition
ABHD12 p.Arg186Cys Uncertain significance ★★ ⚠ same condition
ABHD12 p.Arg218Pro Uncertain significance ★★ ⚠ same condition
ABHD12 p.Arg258Cys Uncertain significance ★★ ⚠ same condition

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/abhd12-p-arg181ser (accessed [today's date]).

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