Is NPHP1 p.Trp381Gly (c.1141T>G) pathogenic?

NPHP1 p.Trp381Gly (c.1141T>G) is classified Conflicting classifications of pathogenicity in NPHP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-20). AlphaMissense: likely pathogenic (0.9205); Absent from gnomAD v4.1; Associated with nephronophthisis 1.

What condition is associated with NPHP1 p.Trp381Gly (c.1141T>G)?

NPHP1 p.Trp381Gly (c.1141T>G) is associated with nephronophthisis 1, Senior-Loken syndrome 1, Joubert syndrome with renal defect (ClinVar).

How common is NPHP1 p.Trp381Gly (c.1141T>G) in the general population?

NPHP1 p.Trp381Gly (c.1141T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NPHP1 p.Trp381Gly (c.1141T>G)?

AlphaMissense predicts likely pathogenic (score 0.9205) — an in-silico prediction, not a clinical call.

NPHP1 p.Trp381Gly

c.1141T>G · rs755958462 · VCV291247

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9205 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9205	likely pathogenic
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -14.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W436G vs ClinVar W381G) — verify the residue.

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: NPHP1
Protein: p.Trp381Gly
Coding: c.1141T>G
MANE Select: NM_001128178
dbSNP: rs755958462
Type: single nucleotide variant
Location: chr2:110150199 (GRCh38)

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

Disease context

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

Also linked: Senior-Loken syndrome 1 Joubert syndrome with renal defect

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-trp381gly (accessed [today's date]).

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