Is ABHD12 p.Pro382Ser (c.1144C>T) pathogenic?

ABHD12 p.Pro382Ser (c.1144C>T) is classified Uncertain significance in ABHD12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). AlphaMissense: likely benign (0.2624); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABHD12 p.Pro382Ser (c.1144C>T)?

ABHD12 p.Pro382Ser (c.1144C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD12 p.Pro382Ser (c.1144C>T) in the general population?

ABHD12 p.Pro382Ser (c.1144C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about ABHD12 p.Pro382Ser (c.1144C>T)?

AlphaMissense predicts likely benign (score 0.2624) — an in-silico prediction, not a clinical call.

ABHD12 p.Pro382Ser

c.1144C>T · rs991573752 · VCV1365099

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2624	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	23.9	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 0.00833% Admixed American · 5/60,002 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,613,354 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
African / African-American	0.00267%	37,461

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: ABHD12
Protein: p.Pro382Ser
Coding: c.1144C>T
MANE Select: NM_001042472
dbSNP: rs991573752
Type: single nucleotide variant
Location: chr20:25302232 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 382: a UniProt-annotated variant site (in pharc); a UniProt-annotated variant site (in pharc; uncertain significance); a UniProt-annotated variant site (in pharc; abolished monoacyglycerol lipase activity)

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.Pro382Leu Uncertain significance ★★ ⚠ same residue
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

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-pro382ser (accessed [today's date]).

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