Is ABHD12 p.Pro334Thr (c.1000C>A) pathogenic?

ABHD12 p.Pro334Thr (c.1000C>A) is classified Likely benign in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-03). AlphaMissense: likely benign (0.1172); Ultra-rare (popmax 0.0245%, eas).

How common is ABHD12 p.Pro334Thr (c.1000C>A) in the general population?

ABHD12 p.Pro334Thr (c.1000C>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about ABHD12 p.Pro334Thr (c.1000C>A)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

ABHD12 p.Pro334Thr

c.1000C>A · rs764697555 · VCV1542346

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	21.9	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 0.0245% East Asian · 11/44,884 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000682% 11/1,613,872 alleles · ultra-rare

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.Pro334Thr
Coding: c.1000C>A
MANE Select: NM_001042472
dbSNP: rs764697555
Type: single nucleotide variant
Location: chr20:25303579 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 334: 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

Similar variants

ABHD12 p.Pro334Leu Uncertain significance ★ ⚠ same residue
ABHD12 p.Pro334= Likely benign ★ same residue
ABHD12 c.1029+1G>T Likely pathogenic ★★ same type
ABHD12 p.Arg262Ter Pathogenic ★★ same type
ABHD12 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
ABHD12 p.Arg352Ter Pathogenic ★★ same type
ABHD12 p.Arg355Ter Pathogenic ★★ same type
ABHD12 c.620-3C>T 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/abhd12-p-pro334thr (accessed [today's date]).

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