Is ABHD2 p.Leu5Val (c.13C>G) pathogenic?

ABHD2 p.Leu5Val (c.13C>G) is classified Uncertain significance in ABHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0648); Very rare (popmax 0.00333%, amr).

How common is ABHD2 p.Leu5Val (c.13C>G) in the general population?

ABHD2 p.Leu5Val (c.13C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABHD2 p.Leu5Val (c.13C>G)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

ABHD2 p.Leu5Val

c.13C>G · VCV4636328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.81	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 3	GERP 0.94, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 79 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	17.54	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 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,762 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: ABHD2
Protein: p.Leu5Val
Coding: c.13C>G
MANE Select: NM_152924
Type: single nucleotide variant
Location: chr15:89116340 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 91.06

Full ABHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD2 p.His312= Benign ★★ same type
ABHD2 p.Tyr400= Benign ★★ same type
ABHD2 p.Val420= Benign ★★ same type
ABHD2 p.Ala222Gly Uncertain significance ★ ⚠ same type
ABHD2 p.Ala274Thr Uncertain significance ★ ⚠ same type
ABHD2 p.Arg175Cys Uncertain significance ★ ⚠ same type
ABHD2 p.Arg254Gln Uncertain significance ★ ⚠ same type
ABHD2 p.Arg293Gln 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/abhd2-p-leu5val (accessed [today's date]).

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