Is ABHD5 p.Ile322Val (c.964A>G) pathogenic?

ABHD5 p.Ile322Val (c.964A>G) is classified Uncertain significance in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.081); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with ABHD5 p.Ile322Val (c.964A>G)?

ABHD5 p.Ile322Val (c.964A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABHD5 p.Ile322Val (c.964A>G) in the general population?

ABHD5 p.Ile322Val (c.964A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ABHD5 p.Ile322Val (c.964A>G)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

ABHD5 p.Ile322Val

c.964A>G · VCV3788492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.455	indeterminate
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	23.0	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 0.033% Middle Eastern · 2/6,058 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000616% 9/1,461,712 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,029
South Asian	0.00329%	30,357
European (non-Finnish)	0.000339%	294,975

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: ABHD5
Protein: p.Ile322Val
Coding: c.964A>G
MANE Select: NM_016006
Type: single nucleotide variant
Location: chr3:43718446 (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-ile322val (accessed [today's date]).

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