Is INPP5E p.Ser11= (c.33C>G) pathogenic?

INPP5E p.Ser11= (c.33C>G) is classified Benign in INPP5E (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 1.

What condition is associated with INPP5E p.Ser11= (c.33C>G)?

INPP5E p.Ser11= (c.33C>G) is associated with Joubert syndrome 1, Joubert syndrome (ClinVar).

INPP5E p.Ser11=

Q: How common is INPP5E p.Ser11= (c.33C>G) in the general population?

INPP5E p.Ser11= (c.33C>G) is common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.33C>G · rs79161998 · VCV129273

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Joubert syndrome 1

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 -0.8	GERP -1.7
Overall
CADD	1.153	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.98% African / African-American · 5,431/68,020 alleles

Filtering AF 7.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.73%

Overall 0.456% 6,678/1,463,608 alleles · common exomes 3,200/1,311,480 · genomes 3,478/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.98%	13
Remaining individualsnot grpmax-eligible	0.835%	120
Middle Eastern	0.79%	127
Admixed American	0.701%	143
East Asian	0.36%	278
South Asian	0.0358%	2,791
European (non-Finnish)	0.0277%	3,605
Finnishnot grpmax-eligible	0.00456%	21,926

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.Ser11=
Coding: c.33C>G
MANE Select: NM_019892
dbSNP: rs79161998
Type: single nucleotide variant
Location: chr9:136439387 (GRCh38)
Structure: AlphaFold pLDDT 88.46

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

Disease context

Joubert syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome

Similar variants

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.Arg563His Likely pathogenic ★★ ⚠ same condition
INPP5E p.Arg585Cys Pathogenic/Likely pathogenic ★★ same condition
INPP5E p.Arg621Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
INPP5E p.Arg621Trp 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-ser11 (accessed [today's date]).

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