Is IMPDH1 p.Ser63= (c.189A>G) pathogenic?

IMPDH1 p.Ser63= (c.189A>G) is classified Conflicting classifications of pathogenicity in IMPDH1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-26). Rare (popmax 0.105%, nfe); Associated with retinitis pigmentosa.

What condition is associated with IMPDH1 p.Ser63= (c.189A>G)?

IMPDH1 p.Ser63= (c.189A>G) is associated with retinitis pigmentosa, Leber congenital amaurosis 11 (ClinVar).

How common is IMPDH1 p.Ser63= (c.189A>G) in the general population?

IMPDH1 p.Ser63= (c.189A>G) is rare (popmax 0.105%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

IMPDH1 p.Ser63=

c.189A>G · rs143796089 · VCV767199

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, nfe)

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 -0.19	GERP -1.2, phastCons 0.005
Overall
CADD	15.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% European (non-Finnish) · 1,241/1,180,006 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0983%

Overall 0.0826% 1,333/1,614,214 alleles · rare exomes 1,242/1,461,854 · genomes 91/152,360 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.105%	951
Remaining individualsnot grpmax-eligible	0.072%	1,389
Admixed American	0.0333%	3,002
African / African-American	0.0266%	3,754
Finnishnot grpmax-eligible	0.00937%	10,674
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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: IMPDH1
Protein: p.Ser63=
Coding: c.189A>G
MANE Select: NM_000883
dbSNP: rs143796089
Type: single nucleotide variant
Location: chr7:128409442 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.71 · 18 PDB
Residue 63: a β-strand

Full IMPDH1 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

Also linked: Leber congenital amaurosis 11

For Retinitis pigmentosa (Orphanet):

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

Similar variants

IMPDH1 p.Lys323Arg Pathogenic/Likely pathogenic ★★ same condition
IMPDH1 c.1075-3C>T Uncertain significance ★★ same condition
IMPDH1 c.*137G>C Uncertain significance ★★ same condition
IMPDH1 c.*721G>A Uncertain significance ★★ same condition
IMPDH1 p.Arg142Trp Uncertain significance ★★ same condition
IMPDH1 p.Arg246Gln Uncertain significance ★★ same condition
IMPDH1 p.Gly530Asp Uncertain significance ★★ same condition
IMPDH1 p.Ter600Trp 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/impdh1-p-ser63 (accessed [today's date]).

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