Is IMPG2 p.Asp1004Val (c.3011A>T) pathogenic?

IMPG2 p.Asp1004Val (c.3011A>T) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-03). AlphaMissense: likely pathogenic (0.8803); Absent from gnomAD v4.1.

How common is IMPG2 p.Asp1004Val (c.3011A>T) in the general population?

IMPG2 p.Asp1004Val (c.3011A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPG2 p.Asp1004Val (c.3011A>T)?

AlphaMissense predicts likely pathogenic (score 0.8803) — an in-silico prediction, not a clinical call.

IMPG2 p.Asp1004Val

c.3011A>T · rs1706422827 · VCV1004659

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8803	likely pathogenic · top 6% in IMPG2
REVEL	0.638	indeterminate
SaProt	LLR -13.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: IMPG2
Protein: p.Asp1004Val
Coding: c.3011A>T
MANE Select: NM_016247
dbSNP: rs1706422827
Type: single nucleotide variant
Location: chr3:101242699 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1004: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 2 domain

Full IMPG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IMPG2 p.Asp1004Gly Uncertain significance ★ ⚠ same residue
IMPG2 c.1240-1G>A Likely pathogenic ★★ same type
IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.502-2A>G Likely pathogenic ★★ same type
IMPG2 c.583+1G>C Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.828+1G>A Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.829-1G>T Pathogenic/Likely pathogenic ★★ 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/impg2-p-asp1004val (accessed [today's date]).

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