Is ABHD5 p.Val196Asp (c.587T>A) pathogenic?

ABHD5 p.Val196Asp (c.587T>A) is classified Uncertain significance in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.8565); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABHD5 p.Val196Asp (c.587T>A)?

ABHD5 p.Val196Asp (c.587T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD5 p.Val196Asp (c.587T>A) in the general population?

ABHD5 p.Val196Asp (c.587T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD5 p.Val196Asp (c.587T>A)?

AlphaMissense predicts likely pathogenic (score 0.8565) — an in-silico prediction, not a clinical call.

ABHD5 p.Val196Asp

c.587T>A · VCV3789043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8565 · 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	0.8565	likely pathogenic
REVEL	0.532	indeterminate
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	24.6	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: ABHD5
Protein: p.Val196Asp
Coding: c.587T>A
MANE Select: NM_016006
Type: single nucleotide variant
Location: chr3:43711789 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62

Full ABHD5 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

ABHD5 p.Asp12Asn Uncertain significance ★★ ⚠ same condition
ABHD5 p.Cys140Gly Uncertain significance ★★ ⚠ same condition
ABHD5 p.Glu133Asp Uncertain significance ★★ ⚠ same condition
ABHD5 p.Glu5Ala Uncertain significance ★★ ⚠ same condition
ABHD5 p.Ile320Thr Uncertain significance ★★ ⚠ same condition
ABHD5 p.Leu214Ile Uncertain significance ★★ ⚠ same condition
ABHD5 p.Lys342Arg Uncertain significance ★★ ⚠ same condition
ABHD5 p.Pro118Thr 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/abhd5-p-val196asp (accessed [today's date]).

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