Is IMPG2 p.Asp324= (c.972C>T) pathogenic?

IMPG2 p.Asp324= (c.972C>T) is classified Conflicting classifications of pathogenicity in IMPG2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0493%, mid); Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Asp324= (c.972C>T)?

IMPG2 p.Asp324= (c.972C>T) is associated with retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Asp324= (c.972C>T) in the general population?

IMPG2 p.Asp324= (c.972C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

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

IMPG2 p.Asp324=

c.972C>T · rs762052051 · VCV901981

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 2.6	GERP 0.1, phastCons 1
Overall
CADD	7.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,080 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.00465% 75/1,613,218 alleles · ultra-rare exomes 65/1,461,132 · genomes 10/152,086 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.2%	501
Middle Easterngrpmax	0.0493%	2,027
Remaining individualsnot grpmax-eligible	0.0128%	7,806
European (non-Finnish)	0.000424%	235,904

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp324=
Coding: c.972C>T
MANE Select: NM_016247
dbSNP: rs762052051
Type: single nucleotide variant
Location: chr3:101257710 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 324: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 1 domain

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.Asp324His Uncertain significance ★★ ⚠ same residue
IMPG2 p.Asp324Asn Uncertain significance ★ same residue
IMPG2 p.Asp324Glu Uncertain significance ★ ⚠ same residue
IMPG2 p.Asp324Val Uncertain significance ★ ⚠ 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

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-asp324 (accessed [today's date]).

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