Is IMPG2 p.Ala243Pro (c.727G>C) pathogenic?

IMPG2 p.Ala243Pro (c.727G>C) is classified Conflicting classifications of pathogenicity in IMPG2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-11-11). AlphaMissense: likely pathogenic (0.972); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with IMPG2 p.Ala243Pro (c.727G>C)?

IMPG2 p.Ala243Pro (c.727G>C) is associated with inherited retinal dystrophy, vitelliform macular dystrophy 5 (ClinVar).

How common is IMPG2 p.Ala243Pro (c.727G>C) in the general population?

IMPG2 p.Ala243Pro (c.727G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IMPG2 p.Ala243Pro (c.727G>C)?

AlphaMissense predicts likely pathogenic (score 0.972) — an in-silico prediction, not a clinical call.

IMPG2 p.Ala243Pro

c.727G>C · rs1706811719 · VCV866736

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.972	likely pathogenic · top 3% in IMPG2
REVEL	0.215	benign-leaning
SaProt	LLR -14.26	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 7.6	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	25.7	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.Ala243Pro
Coding: c.727G>C
MANE Select: NM_016247
dbSNP: rs1706811719
Type: single nucleotide variant
Location: chr3:101273682 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 243: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); a UniProt-annotated variant site (found in a patient with vitelliform macular dystrophy; uncertain significance); the sea 1 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: vitelliform macular dystrophy 5

Similar variants

IMPG2 p.Ala243Glu Uncertain significance ★★ ⚠ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg906Ter Pathogenic ★★ same condition
IMPG2 p.Arg964Ter Pathogenic ★★ same condition
IMPG2 p.Gln363Ter Pathogenic ★★ same condition
IMPG2 p.Gln814Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Gln856Ter Pathogenic ★★ same condition
IMPG2 p.Glu1164Ter Pathogenic/Likely pathogenic ★★ 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-ala243pro (accessed [today's date]).

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