Is ABHD12 p.Pro169Arg (c.506C>G) pathogenic?

ABHD12 p.Pro169Arg (c.506C>G) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.2749); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABHD12 p.Pro169Arg (c.506C>G)?

ABHD12 p.Pro169Arg (c.506C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD12 p.Pro169Arg (c.506C>G) in the general population?

ABHD12 p.Pro169Arg (c.506C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD12 p.Pro169Arg (c.506C>G)?

AlphaMissense predicts likely benign (score 0.2749) — an in-silico prediction, not a clinical call.

ABHD12 p.Pro169Arg

c.506C>G · VCV3782753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2749 · 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	0.2749	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -12.63	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	28.3	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.Pro169Arg
Coding: c.506C>G
MANE Select: NM_001042472
Type: single nucleotide variant
Location: chr20:25320235 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 169: 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.Pro169Ala 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-pro169arg (accessed [today's date]).

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