Is IMPG2 p.Val576= (c.1728C>G) pathogenic?

IMPG2 p.Val576= (c.1728C>G) is classified Conflicting classifications of pathogenicity in IMPG2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-24). Very rare (popmax 0.00887%, nfe); Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Val576= (c.1728C>G)?

IMPG2 p.Val576= (c.1728C>G) is associated with retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Val576= (c.1728C>G) in the general population?

IMPG2 p.Val576= (c.1728C>G) is very rare (popmax 0.00887%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

IMPG2 p.Val576=

c.1728C>G · rs556074974 · VCV900268

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00887%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -0.91, phastCons 0.95
Overall
CADD	3.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00887% European (non-Finnish) · 104/1,173,070 alleles

Filtering AF 0.00745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00696%

Overall 0.00682% 109/1,598,764 alleles · very rare exomes 96/1,446,486 · genomes 13/152,278 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00887%	11,280
Remaining individualsnot grpmax-eligible	0.00324%	30,831
African / African-American	0.0027%	37,100
East Asian	0.00224%	44,710

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IMPG2
Protein: p.Val576=
Coding: c.1728C>G
MANE Select: NM_016247
dbSNP: rs556074974
Type: single nucleotide variant
Location: chr3:101244603 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 576: 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.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
IMPG2 p.Ala698Val Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala978Val Uncertain significance ★★ ⚠ same condition
IMPG2 p.Glu1235Gln 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-val576 (accessed [today's date]).

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