Is INPP5E p.Pro191Arg (c.572C>G) pathogenic?

INPP5E p.Pro191Arg (c.572C>G) is classified Benign/Likely benign in INPP5E (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0783); Rare (popmax 0.796%, afr); Associated with Joubert syndrome.

What condition is associated with INPP5E p.Pro191Arg (c.572C>G)?

INPP5E p.Pro191Arg (c.572C>G) is associated with Joubert syndrome (ClinVar).

How common is INPP5E p.Pro191Arg (c.572C>G) in the general population?

INPP5E p.Pro191Arg (c.572C>G) is rare (popmax 0.796%, afr) (gnomAD).

What do computational predictors say about INPP5E p.Pro191Arg (c.572C>G)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

INPP5E p.Pro191Arg

c.572C>G · rs61734181 · VCV129263

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.796%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.34	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 3.4	GERP -0.33, phastCons 0.48
Overall
CADD	14.68	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 0.796% African / African-American · 596/74,862 alleles

Filtering AF 0.743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.722%

Overall 0.0437% 701/1,604,614 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.796%	126
Remaining individualsnot grpmax-eligible	0.0596%	1,677
Admixed American	0.034%	2,942
Middle Eastern	0.0331%	3,024
European (non-Finnish)	0.00383%	26,137
South Asian	0.00111%	90,220

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: INPP5E
Protein: p.Pro191Arg
Coding: c.572C>G
MANE Select: NM_015160 · reported on NM_019892
dbSNP: rs61734181
Type: single nucleotide variant
Location: chr9:136438848 (GRCh38)
Structure: AlphaFold pLDDT 88.46

Full INPP5E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INPP5E p.Pro191Leu Uncertain significance ★ ⚠ same residue
INPP5E p.Pro191Ala Uncertain significance ★ ⚠ same residue
INPP5E p.Arg378Cys Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg435Gln Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg435Trp Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg557His Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg585Cys Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg621Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/inpp5e-p-pro191arg (accessed [today's date]).

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