Is INPP5E p.Asp490= (c.1470C>T) pathogenic?

INPP5E p.Asp490= (c.1470C>T) is classified Benign/Likely benign in INPP5E (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0506%, sas); Associated with Joubert syndrome.

What condition is associated with INPP5E p.Asp490= (c.1470C>T)?

INPP5E p.Asp490= (c.1470C>T) is associated with Joubert syndrome (ClinVar).

How common is INPP5E p.Asp490= (c.1470C>T) in the general population?

INPP5E p.Asp490= (c.1470C>T) is ultra-rare (popmax 0.0506%, sas) (gnomAD).

INPP5E p.Asp490=

c.1470C>T · rs375301475 · VCV461746

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0506%, sas)

Conditions

Joubert syndrome

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 -0.64	GERP -3, phastCons 0.001
Overall
CADD	5.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0506% South Asian · 46/90,930 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0348%

Overall 0.00726% 117/1,610,670 alleles · ultra-rare exomes 94/1,460,222 · genomes 23/150,448 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0506%	1,977
African / African-American	0.0417%	2,397
East Asian	0.00671%	14,905
Remaining individualsnot grpmax-eligible	0.00641%	15,606
Finnishnot grpmax-eligible	0.0032%	31,266
European (non-Finnish)	0.00254%	39,314
Admixed American	0.00167%	59,818

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.Asp490=
Coding: c.1470C>T
MANE Select: NM_019892
dbSNP: rs375301475
Type: single nucleotide variant
Location: chr9:136431903 (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.Asp490Tyr Conflicting classifications of pathogenicity ★ same residue
INPP5E p.Asp490Val 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-asp490 (accessed [today's date]).

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