Is ABHD12 p.Ala252Val (c.755C>T) pathogenic?

ABHD12 p.Ala252Val (c.755C>T) is classified Likely pathogenic in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-30). AlphaMissense: likely pathogenic (0.9342); Very rare (popmax 0.00446%, eas); Associated with ABHD12-related disorder.

What condition is associated with ABHD12 p.Ala252Val (c.755C>T)?

ABHD12 p.Ala252Val (c.755C>T) is associated with ABHD12-related disorder (ClinVar).

How common is ABHD12 p.Ala252Val (c.755C>T) in the general population?

ABHD12 p.Ala252Val (c.755C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ABHD12 p.Ala252Val (c.755C>T)?

AlphaMissense predicts likely pathogenic (score 0.9342) — an in-silico prediction, not a clinical call.

ABHD12 p.Ala252Val

c.755C>T · rs1300228825 · VCV866325

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABHD12-related disorder

Computational evidence

Protein change
AlphaMissense	0.9342	likely pathogenic ✓ concordant with ClinVar
REVEL	0.282	benign-leaning
SaProt	LLR -13.25	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	27.7	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 0.00446% East Asian · 2/44,856 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000497% 8/1,610,786 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,428
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,488
South Asian	0.00221%	45,212
European (non-Finnish)	0.000255%	392,845

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.Ala252Val
Coding: c.755C>T
MANE Select: NM_001042472
dbSNP: rs1300228825
Type: single nucleotide variant
Location: chr20:25308489 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 252: 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

ABHD12-related disorder

Similar variants

ABHD12 p.Arg262Ter Pathogenic ★★ same condition
ABHD12 p.Arg352Ter Pathogenic ★★ same condition
ABHD12 p.Arg355Ter Pathogenic ★★ same condition
ABHD12 c.1157+1G>A Likely pathogenic ★ same condition
ABHD12 c.316+1G>A Likely pathogenic ★ same condition
ABHD12 p.Arg65Ter Pathogenic ★ same condition
ABHD12 p.Gln153Ter Likely pathogenic ★ same condition
ABHD12 p.Glu134Ter Likely pathogenic ★ 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-ala252val (accessed [today's date]).

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