Is IMPG2 p.Leu19= (c.57G>C) pathogenic?

IMPG2 p.Leu19= (c.57G>C) is classified Conflicting classifications of pathogenicity in IMPG2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-24). Rare (popmax 0.223%, sas); Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Leu19= (c.57G>C)?

IMPG2 p.Leu19= (c.57G>C) is associated with retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Leu19= (c.57G>C) in the general population?

IMPG2 p.Leu19= (c.57G>C) is rare (popmax 0.223%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

IMPG2 p.Leu19=

c.57G>C · rs188916371 · VCV342359

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.223%, sas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 1
Overall
CADD	6.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% South Asian · 203/90,848 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.189%

Overall 0.0282% 453/1,604,376 alleles · rare exomes 428/1,452,244 · genomes 25/152,132 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.223%	448
Middle Eastern	0.166%	602
Remaining individualsnot grpmax-eligible	0.0354%	2,823
European (non-Finnish)	0.0175%	5,717
Admixed American	0.01%	9,958
African / African-American	0.00535%	18,686
Finnishnot grpmax-eligible	0.00469%	21,310

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.Leu19=
Coding: c.57G>C
MANE Select: NM_016247
dbSNP: rs188916371
Type: single nucleotide variant
Location: chr3:101320316 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28

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.Leu19Pro 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
IMPG2 p.Ala1129Gly Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala698Val Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala978Val 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-leu19 (accessed [today's date]).

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