Is NPHP4 p.Asp276= (c.828C>T) pathogenic?

NPHP4 p.Asp276= (c.828C>T) is classified Likely benign in NPHP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-28). Ultra-rare (popmax 0.0278%, eas); Associated with nephronophthisis 4.

What condition is associated with NPHP4 p.Asp276= (c.828C>T)?

NPHP4 p.Asp276= (c.828C>T) is associated with nephronophthisis 4, Senior-Loken syndrome 4, nephronophthisis (ClinVar).

How common is NPHP4 p.Asp276= (c.828C>T) in the general population?

NPHP4 p.Asp276= (c.828C>T) is ultra-rare (popmax 0.0278%, eas) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP4 p.Asp276=

c.828C>T · rs765113652 · VCV1580824

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0278%, eas)

Conditions

nephronophthisis 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -4.2
Overall
CADD	0.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0278% East Asian · 12/43,238 alleles

Filtering AF 0.0159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00494% 78/1,578,820 alleles · ultra-rare exomes 69/1,426,616 · genomes 9/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0278%	3,603
Ashkenazi Jewishnot grpmax-eligible	0.0138%	7,256
European (non-Finnish)	0.00489%	20,449
Remaining individualsnot grpmax-eligible	0.00325%	30,753
African / African-American	0.0027%	37,101
South Asian	0.00114%	87,518

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: NPHP4
Protein: p.Asp276=
Coding: c.828C>T
MANE Select: NM_015102
dbSNP: rs765113652
Type: single nucleotide variant
Location: chr1:5948234 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Senior-Loken syndrome 4 nephronophthisis

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP4 c.2304+1G>A Pathogenic ★★ same condition
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.2611+1G>C Pathogenic ★★ same condition
NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.517+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.518-2A>G Likely pathogenic ★★ same condition
NPHP4 c.992+2T>C 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/nphp4-p-asp276 (accessed [today's date]).

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