Is NPHP1 p.His478fs (c.1431_1432insTACCA) pathogenic?

NPHP1 p.His478fs (c.14311432insTACCA) is classified Likely pathogenic in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-28). No gnomAD frequency available for this variant; Associated with Joubert syndrome with renal defect.

What condition is associated with NPHP1 p.His478fs (c.1431_1432insTACCA)?

NPHP1 p.His478fs (c.1431_1432insTACCA) is associated with Joubert syndrome with renal defect (ClinVar).

How common is NPHP1 p.His478fs (c.1431_1432insTACCA) in the general population?

NPHP1 p.His478fs (c.1431_1432insTACCA) is no gnomAD frequency available for this variant (gnomAD).

NPHP1 p.His478fs

c.1431_1432insTACCA · rs2467238709 · VCV2677277

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Joubert syndrome with renal defect

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.89, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHP1
Protein: p.His478fs
Coding: c.1431_1432insTACCA
MANE Select: NM_001128178
dbSNP: rs2467238709
Type: Insertion
Location: chr2:110144492 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

NPHP1 p.His478= Likely benign ★★ same residue
NPHP1 p.His478Arg Uncertain significance ⚠ same residue
NPHP1 c.1083+1G>A Likely pathogenic ★★ same condition
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.141_143+40del Likely pathogenic ★★ same condition
NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
NPHP1 c.144-1G>A 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/nphp1-p-his478fs (accessed [today's date]).

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