Is IMPG2 p.Arg1078Ser (c.3234G>T) pathogenic?

IMPG2 p.Arg1078Ser (c.3234G>T) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-27). AlphaMissense: likely pathogenic (0.9468); Absent from gnomAD v4.1.

How common is IMPG2 p.Arg1078Ser (c.3234G>T) in the general population?

IMPG2 p.Arg1078Ser (c.3234G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPG2 p.Arg1078Ser (c.3234G>T)?

AlphaMissense predicts likely pathogenic (score 0.9468) — an in-silico prediction, not a clinical call.

IMPG2 p.Arg1078Ser

c.3234G>T · rs1553680151 · VCV546940

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9468 · 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	0.9468	likely pathogenic · top 4% in IMPG2
REVEL	0.349	indeterminate
SaProt	LLR -11.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.70	acceptor loss · deltas
Pangolin	Δ0.58	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.012	GERP -2.1, phastCons 0.92
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	19.94	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.Arg1078Ser
Coding: c.3234G>T
MANE Select: NM_016247
dbSNP: rs1553680151
Type: single nucleotide variant
Location: chr3:101231145 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1078: 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.Arg1078= Uncertain significance ★ same residue
IMPG2 p.Arg1078Lys 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-arg1078ser (accessed [today's date]).

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