Is NPHP1 p.Leu571Pro (c.1712T>C) pathogenic?

NPHP1 p.Leu571Pro (c.1712T>C) is classified Uncertain significance in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). AlphaMissense: likely pathogenic (0.9435); Absent from gnomAD v4.1; Associated with NPHP1-related disorder.

What condition is associated with NPHP1 p.Leu571Pro (c.1712T>C)?

NPHP1 p.Leu571Pro (c.1712T>C) is associated with NPHP1-related disorder (ClinVar).

How common is NPHP1 p.Leu571Pro (c.1712T>C) in the general population?

NPHP1 p.Leu571Pro (c.1712T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NPHP1 p.Leu571Pro (c.1712T>C)?

AlphaMissense predicts likely pathogenic (score 0.9435) — an in-silico prediction, not a clinical call.

NPHP1 p.Leu571Pro

c.1712T>C · rs2467154694 · VCV2630911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9435 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NPHP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9435	likely pathogenic · top 2% in NPHP1
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -16.26	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L626P vs ClinVar L571P) — 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.Leu571Pro
Coding: c.1712T>C
MANE Select: NM_001128178
dbSNP: rs2467154694
Type: single nucleotide variant
Location: chr2:110129190 (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

NPHP1-related disorder

Similar variants

NPHP1 p.Leu571Phe Uncertain significance ★ ⚠ same residue
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.771+58C>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Trp575Ter Likely pathogenic ★★ same condition
NPHP1 p.Tyr294Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Glu142Asp Uncertain significance ★★ ⚠ same condition
NPHP1 c.771+41A>G Uncertain significance ★ ⚠ 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-leu571pro (accessed [today's date]).

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