Is IMPG2 p.Ile412Val (c.1234A>G) pathogenic?

IMPG2 p.Ile412Val (c.1234A>G) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0707); Very rare (popmax 6.21e-05%); Associated with Inborn genetic diseases.

What condition is associated with IMPG2 p.Ile412Val (c.1234A>G)?

IMPG2 p.Ile412Val (c.1234A>G) is associated with Inborn genetic diseases (ClinVar).

How common is IMPG2 p.Ile412Val (c.1234A>G) in the general population?

IMPG2 p.Ile412Val (c.1234A>G) is very rare (popmax 6.21e-05%) (gnomAD).

What do computational predictors say about IMPG2 p.Ile412Val (c.1234A>G)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

IMPG2 p.Ile412Val

c.1234A>G · VCV4038583

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.21e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -5.5
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	0.046	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 6.21e-05%

Overall 6.21e-05% 1/1,609,606 alleles · very rare exomes 1/1,457,404 · genomes 0/152,202 · joint denominator

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: IMPG2
Protein: p.Ile412Val
Coding: c.1234A>G
MANE Select: NM_016247
Type: single nucleotide variant
Location: chr3:101253701 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 412: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)

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.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
IMPG2 p.Ala419Asp Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala741Asp Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala978Thr Uncertain significance ★★ ⚠ same condition
IMPG2 p.Arg1048Gln 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-ile412val (accessed [today's date]).

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