Is IMPG2 p.Pro1147Ser (c.3439C>T) pathogenic?

IMPG2 p.Pro1147Ser (c.3439C>T) is classified Conflicting classifications of pathogenicity in IMPG2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0995); Common (popmax 6.64%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Pro1147Ser (c.3439C>T)?

IMPG2 p.Pro1147Ser (c.3439C>T) 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.

What do computational predictors say about IMPG2 p.Pro1147Ser (c.3439C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

IMPG2 p.Pro1147Ser

Q: How common is IMPG2 p.Pro1147Ser (c.3439C>T) in the general population?

IMPG2 p.Pro1147Ser (c.3439C>T) is common (popmax 6.64%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3439C>T · rs111784356 · VCV191179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.64%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -4.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -0.2, phastCons 0.85
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	13.18	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.64% African / African-American · 4,982/75,008 alleles

Filtering AF 6.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.42%

Overall 0.358% 5,780/1,613,846 alleles · common exomes 2,955/1,461,566 · genomes 2,825/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.64%	15
Remaining individualsnot grpmax-eligible	0.498%	201
Admixed American	0.482%	208
Middle Eastern	0.434%	231
European (non-Finnish)	0.0136%	7,374
South Asian	0.0132%	7,590

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.Pro1147Ser
Coding: c.3439C>T
MANE Select: NM_016247
dbSNP: rs111784356
Type: single nucleotide variant
Location: chr3:101229574 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1147: 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.Pro1147Arg 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-pro1147ser (accessed [today's date]).

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