Is IMPG2 p.Asp588Ala (c.1763A>C) pathogenic?

IMPG2 p.Asp588Ala (c.1763A>C) is classified Uncertain significance in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-30). AlphaMissense: likely benign (0.1117); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Asp588Ala (c.1763A>C)?

IMPG2 p.Asp588Ala (c.1763A>C) is associated with retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Asp588Ala (c.1763A>C) in the general population?

IMPG2 p.Asp588Ala (c.1763A>C) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IMPG2 p.Asp588Ala (c.1763A>C)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

IMPG2 p.Asp588Ala

c.1763A>C · rs746692897 · VCV900267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP 0.32, phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	19.97	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

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.Asp588Ala
Coding: c.1763A>C
MANE Select: NM_016247
dbSNP: rs746692897
Type: single nucleotide variant
Location: chr3:101244568 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 588: 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

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IMPG2 p.Asp588Gly Uncertain significance ★ ⚠ same residue
IMPG2 p.Asp588Val Uncertain significance ★ ⚠ same residue
IMPG2 p.Asp588= Likely benign ★ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Trp758Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.*2658G>T Uncertain significance ★★ same condition
IMPG2 c.*426G>A Uncertain significance ★★ same condition
IMPG2 p.Ala1129Gly 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-asp588ala (accessed [today's date]).

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