Is IMPG2 p.Arg1080Pro (c.3239G>C) pathogenic?

IMPG2 p.Arg1080Pro (c.3239G>C) is classified Uncertain significance in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-10). AlphaMissense: likely pathogenic (0.7797); Absent from gnomAD v4.1.

How common is IMPG2 p.Arg1080Pro (c.3239G>C) in the general population?

IMPG2 p.Arg1080Pro (c.3239G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPG2 p.Arg1080Pro (c.3239G>C)?

AlphaMissense predicts likely pathogenic (score 0.7797) — an in-silico prediction, not a clinical call.

IMPG2 p.Arg1080Pro

c.3239G>C · rs777459431 · VCV962338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7797 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7797	likely pathogenic · top 9% in IMPG2
REVEL	0.259	benign-leaning
SaProt	LLR -12.90	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	23.3	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.Arg1080Pro
Coding: c.3239G>C
MANE Select: NM_016247
dbSNP: rs777459431
Type: single nucleotide variant
Location: chr3:101231140 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1080: the 'hyaluronan-binding motif involved in chondroitin sulfate c-binding' region; a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the egf-like 2 domain

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

Similar variants

IMPG2 p.Arg1080Gln Uncertain significance ★★ ⚠ same residue
IMPG2 p.Arg1080Trp 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

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-arg1080pro (accessed [today's date]).

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