Is ABHD12 p.Pro7Leu (c.20C>T) pathogenic?

ABHD12 p.Pro7Leu (c.20C>T) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.0896); Very rare (popmax 0.000645%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABHD12 p.Pro7Leu (c.20C>T)?

ABHD12 p.Pro7Leu (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD12 p.Pro7Leu (c.20C>T) in the general population?

ABHD12 p.Pro7Leu (c.20C>T) is very rare (popmax 0.000645%, nfe) (gnomAD).

What do computational predictors say about ABHD12 p.Pro7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

ABHD12 p.Pro7Leu

c.20C>T · VCV3992686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000645%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.27	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 7.8	GERP -0.44, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000645% European (non-Finnish) · 7/1,085,242 alleles

Filtering AF 0.000268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000173%

Overall 0.000494% 7/1,416,074 alleles · very 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.Pro7Leu
Coding: c.20C>T
MANE Select: NM_001042472
Type: single nucleotide variant
Location: chr20:25390684 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60

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.Pro7Ser 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-pro7leu (accessed [today's date]).

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