Is IMPG2 p.Arg127Pro (c.380G>C) pathogenic?

IMPG2 p.Arg127Pro (c.380G>C) is classified Likely pathogenic in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-17). AlphaMissense: likely pathogenic (0.9911); Absent from gnomAD v4.1; Associated with vitelliform macular dystrophy 5.

What condition is associated with IMPG2 p.Arg127Pro (c.380G>C)?

IMPG2 p.Arg127Pro (c.380G>C) is associated with vitelliform macular dystrophy 5 (ClinVar).

How common is IMPG2 p.Arg127Pro (c.380G>C) in the general population?

IMPG2 p.Arg127Pro (c.380G>C) is absent from gnomAD v4.1 (gnomAD).

How is Adult-onset foveomacular vitelliform dystrophy inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IMPG2 p.Arg127Pro (c.380G>C)?

AlphaMissense predicts likely pathogenic (score 0.9911) — an in-silico prediction, not a clinical call.

IMPG2 p.Arg127Pro

c.380G>C · rs766305807 · VCV191182

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

vitelliform macular dystrophy 5

Computational evidence

Protein change
AlphaMissense	0.9911	likely pathogenic ✓ concordant with ClinVar · top 1% in IMPG2
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -16.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	27.3	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.Arg127Pro
Coding: c.380G>C
MANE Select: NM_016247
dbSNP: rs766305807
Type: single nucleotide variant
Location: chr3:101304267 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 127: a UniProt-annotated variant site (in rp56)

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

Disease context

vitelliform macular dystrophy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adult-onset foveomacular vitelliform dystrophy (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

IMPG2 p.Arg127Ter Pathogenic ★★ same residue
IMPG2 p.Arg127Gln Uncertain significance ★ ⚠ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg906Ter Pathogenic ★★ same condition
IMPG2 p.Phe1016Ser Likely pathogenic ★★ same condition
IMPG2 p.Trp758Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Tyr171Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Ala686Thr 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-arg127pro (accessed [today's date]).

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