Is ABHD12 p.Pro379Ser (c.1135C>T) pathogenic?

ABHD12 p.Pro379Ser (c.1135C>T) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: likely benign (0.2216); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABHD12 p.Pro379Ser (c.1135C>T)?

ABHD12 p.Pro379Ser (c.1135C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD12 p.Pro379Ser (c.1135C>T) in the general population?

ABHD12 p.Pro379Ser (c.1135C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD12 p.Pro379Ser (c.1135C>T)?

AlphaMissense predicts likely benign (score 0.2216) — an in-silico prediction, not a clinical call.

ABHD12 p.Pro379Ser

c.1135C>T · VCV3992695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2216 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2216	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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	28.5	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: ABHD12
Protein: p.Pro379Ser
Coding: c.1135C>T
MANE Select: NM_001042472
Type: single nucleotide variant
Location: chr20:25302241 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 379: 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.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-pro379ser (accessed [today's date]).

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