Is ABHD4 p.Arg115Lys (c.344G>A) pathogenic?

ABHD4 p.Arg115Lys (c.344G>A) is classified Uncertain significance in ABHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.0738); Absent from gnomAD v4.1.

How common is ABHD4 p.Arg115Lys (c.344G>A) in the general population?

ABHD4 p.Arg115Lys (c.344G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD4 p.Arg115Lys (c.344G>A)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

ABHD4 p.Arg115Lys

c.344G>A · VCV3788312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.49	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 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 159 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	20.4	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

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: ABHD4
Protein: p.Arg115Lys
Coding: c.344G>A
MANE Select: NM_022060
Type: single nucleotide variant
Location: chr14:22603621 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30
Residue 115: the ab hydrolase-1 domain

Full ABHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD4 p.Ala230Glu Uncertain significance ★ ⚠ same type
ABHD4 p.Ala2Thr Uncertain significance ★ ⚠ same type
ABHD4 p.Arg132Gln Uncertain significance ★ ⚠ same type
ABHD4 p.Arg185Cys Uncertain significance ★ ⚠ same type
ABHD4 p.Arg185His Uncertain significance ★ ⚠ same type
ABHD4 p.Arg200Cys Uncertain significance ★ ⚠ same type
ABHD4 p.Arg21His Uncertain significance ★ ⚠ same type
ABHD4 p.Arg267Gln 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/abhd4-p-arg115lys (accessed [today's date]).

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