Is INPP5E p.Ser255Phe (c.764C>T) pathogenic?

INPP5E p.Ser255Phe (c.764C>T) is classified Uncertain significance in INPP5E (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.2916); Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with INPP5E p.Ser255Phe (c.764C>T)?

INPP5E p.Ser255Phe (c.764C>T) is associated with Joubert syndrome (ClinVar).

How common is INPP5E p.Ser255Phe (c.764C>T) in the general population?

INPP5E p.Ser255Phe (c.764C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INPP5E p.Ser255Phe (c.764C>T)?

AlphaMissense predicts likely benign (score 0.2916) — an in-silico prediction, not a clinical call.

INPP5E p.Ser255Phe

c.764C>T · rs368817877 · VCV1481084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2916 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.2916	likely benign
REVEL	0.586	indeterminate
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.1, phastCons 1
Overall
CADD	24.6	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.Ser255Phe
Coding: c.764C>T
MANE Select: NM_019892
dbSNP: rs368817877
Type: single nucleotide variant
Location: chr9:136438656 (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.Ser255Tyr Uncertain significance ★★ ⚠ same residue
PMPCA p.Gly255Ser 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-ser255phe (accessed [today's date]).

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