Is IMPG2 p.Asp636= (c.1908T>C) pathogenic?

IMPG2 p.Asp636= (c.1908T>C) is classified Benign/Likely benign in IMPG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 6.61%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Asp636= (c.1908T>C)?

IMPG2 p.Asp636= (c.1908T>C) is associated with retinitis pigmentosa (ClinVar).

How is Retinitis pigmentosa inherited?

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

IMPG2 p.Asp636=

Q: How common is IMPG2 p.Asp636= (c.1908T>C) in the general population?

IMPG2 p.Asp636= (c.1908T>C) is common (popmax 6.61%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1908T>C · rs35648234 · VCV342347

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.61%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.64	GERP -5.2
Overall
CADD	0.432	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.61% African / African-American · 4,962/75,046 alleles

Filtering AF 6.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.4%

Overall 0.355% 5,732/1,614,172 alleles · common exomes 2,924/1,461,842 · genomes 2,808/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.61%	15
Remaining individualsnot grpmax-eligible	0.477%	210
Admixed American	0.458%	218
Middle Eastern	0.413%	242
European (non-Finnish)	0.0136%	7,329
South Asian	0.0121%	8,280

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.Asp636=
Coding: c.1908T>C
MANE Select: NM_016247
dbSNP: rs35648234
Type: single nucleotide variant
Location: chr3:101244423 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 636: 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.Asp636Asn Uncertain significance ★ ⚠ same residue
IMPG2 p.Asp636Glu 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

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-asp636 (accessed [today's date]).

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