Is IMPG2 p.Asp324Glu (c.972C>A) pathogenic?

IMPG2 p.Asp324Glu (c.972C>A) is classified Uncertain significance in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: ambiguous (0.5016); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IMPG2 p.Asp324Glu (c.972C>A)?

IMPG2 p.Asp324Glu (c.972C>A) is associated with Inborn genetic diseases (ClinVar).

How common is IMPG2 p.Asp324Glu (c.972C>A) in the general population?

IMPG2 p.Asp324Glu (c.972C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPG2 p.Asp324Glu (c.972C>A)?

AlphaMissense predicts ambiguous (score 0.5016) — an in-silico prediction, not a clinical call.

IMPG2 p.Asp324Glu

c.972C>A · VCV3860466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5016	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -6.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	19.78	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: IMPG2
Protein: p.Asp324Glu
Coding: c.972C>A
MANE Select: NM_016247
Type: single nucleotide variant
Location: chr3:101257710 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 324: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 1 domain

Full IMPG2 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

IMPG2 p.Asp324His Uncertain significance ★★ ⚠ same residue
IMPG2 p.Asp324Val Uncertain significance ★ ⚠ same residue
IMPG2 p.Asp324= Conflicting classifications of pathogenicity ★ same residue
IMPG2 p.Asp324Asn Uncertain significance ★ same residue
IMPG2 p.Ala1230Ser Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala1231Val Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala207Thr Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala280Ser 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/impg2-p-asp324glu (accessed [today's date]).

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