Is NPHP1 c.771+58C>A pathogenic?

NPHP1 c.771+58C>A is classified Conflicting classifications of pathogenicity in NPHP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-13). Very rare (popmax 0.00755%, nfe); Associated with nephronophthisis.

What condition is associated with NPHP1 c.771+58C>A?

NPHP1 c.771+58C>A is associated with nephronophthisis (ClinVar).

How common is NPHP1 c.771+58C>A in the general population?

NPHP1 c.771+58C>A is very rare (popmax 0.00755%, nfe) (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NPHP1 c.771+58C>A

rs367600757 · VCV255709

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00755%, nfe)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +58	deep intronic (+58 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.1, phastCons 0.001
Non-coding constraint	Z 0.26	1 kb window · o/e 0.98 · regional · uncalibrated
Overall
CADD	1.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00755% European (non-Finnish) · 89/1,178,604 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00564% 91/1,612,284 alleles · very rare exomes 84/1,460,342 · genomes 7/151,942 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00755%	13,243
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
Remaining individualsnot grpmax-eligible	0.0016%	62,436

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: NPHP1
Coding: c.771+58C>A
MANE Select: NM_001128178
dbSNP: rs367600757
Type: single nucleotide variant
Location: chr2:110164630 (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

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

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.329+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.522+1G>A Likely pathogenic ★★ same condition
NPHP1 c.729-2A>G 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-c-771-plus-58c-a (accessed [today's date]).

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