Is INPP5E p.Ser386Pro (c.1156T>C) pathogenic?

INPP5E p.Ser386Pro (c.1156T>C) is classified Likely pathogenic in INPP5E (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-17). AlphaMissense: likely pathogenic (0.9884); Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with INPP5E p.Ser386Pro (c.1156T>C)?

INPP5E p.Ser386Pro (c.1156T>C) is associated with Joubert syndrome, Joubert syndrome and related disorders (ClinVar).

How common is INPP5E p.Ser386Pro (c.1156T>C) in the general population?

INPP5E p.Ser386Pro (c.1156T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INPP5E p.Ser386Pro (c.1156T>C)?

AlphaMissense predicts likely pathogenic (score 0.9884) — an in-silico prediction, not a clinical call.

INPP5E p.Ser386Pro

c.1156T>C · rs771866083 · VCV2042055

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9884 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.9884	likely pathogenic ✓ concordant with ClinVar · top 10% in INPP5E
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Overall
CADD	28.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INPP5E
Protein: p.Ser386Pro
Coding: c.1156T>C
MANE Select: NM_019892
dbSNP: rs771866083
Type: single nucleotide variant
Location: chr9:136433158 (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

Also linked: Joubert syndrome and related disorders

Similar variants

INPP5E p.Ser386Leu 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.Arg563His 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-ser386pro (accessed [today's date]).

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