Is IMPDH2 p.Asp239Val (c.716A>T) pathogenic?

IMPDH2 p.Asp239Val (c.716A>T) is classified Likely pathogenic in IMPDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-03). AlphaMissense: likely pathogenic (0.9611); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with IMPDH2 p.Asp239Val (c.716A>T)?

IMPDH2 p.Asp239Val (c.716A>T) is associated with neurodevelopmental disorder (ClinVar).

How common is IMPDH2 p.Asp239Val (c.716A>T) in the general population?

IMPDH2 p.Asp239Val (c.716A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPDH2 p.Asp239Val (c.716A>T)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

IMPDH2 p.Asp239Val

c.716A>T · VCV4891239

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic ✓ concordant with ClinVar
REVEL	0.932	strongly pathogenic-leaning
SaProt	LLR -17.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 4,964 bp · p 1e-16 · regional, not allelic
Overall
CADD	28.7	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: IMPDH2
Protein: p.Asp239Val
Coding: c.716A>T
MANE Select: NM_000884
Type: single nucleotide variant
Location: chr3:49026790 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07 · 25 PDB

Full IMPDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IMPDH2 p.Asp239His Uncertain significance ★ ⚠ same residue
QRICH1 p.Arg652Ter Pathogenic ★★ same type
IMPDH2 p.Ile88Thr Uncertain significance ★★ ⚠ same type
IMPDH2 c.819+10T>C Benign ★★ same type
IMPDH2 c.99-4G>A Benign/Likely benign ★★ same type
IMPDH2 p.Gly113Glu Likely pathogenic ★ same type
IMPDH2 p.Lys238Arg Likely pathogenic ★ ⚠ same type
IMPDH2 c.147+5G>A 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/impdh2-p-asp239val (accessed [today's date]).

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