Is NPHP1 p.His478= (c.1434C>T) pathogenic?

NPHP1 p.His478= (c.1434C>T) is classified Likely benign in NPHP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Very rare (popmax 0.00892%, eas); Associated with nephronophthisis.

What condition is associated with NPHP1 p.His478= (c.1434C>T)?

NPHP1 p.His478= (c.1434C>T) is associated with nephronophthisis, nephronophthisis 1, Senior-Loken syndrome 1 (ClinVar).

How common is NPHP1 p.His478= (c.1434C>T) in the general population?

NPHP1 p.His478= (c.1434C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP1 p.His478=

c.1434C>T · rs148809478 · VCV531636

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.77 · evaluated, not missing
Pangolin	Δ0.28	gain · loss 0.15 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -2.2	GERP -3.7
Overall
CADD	6.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,860 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00292% 47/1,610,048 alleles · very rare exomes 44/1,457,966 · genomes 3/152,082 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,215
Remaining individualsnot grpmax-eligible	0.00641%	15,591
Admixed American	0.00333%	29,995
South Asian	0.0033%	30,328
European (non-Finnish)	0.00289%	34,605

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
Protein: p.His478=
Coding: c.1434C>T
MANE Select: NM_001128178
dbSNP: rs148809478
Type: single nucleotide variant
Location: chr2:110143637 (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

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

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP1 p.His478fs Likely pathogenic ★ 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.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

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-his478 (accessed [today's date]).

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