Is NPHP4 p.Asp39= (c.117C>T) pathogenic?

NPHP4 p.Asp39= (c.117C>T) is classified Likely benign in NPHP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0867%, afr); Associated with nephronophthisis.

What condition is associated with NPHP4 p.Asp39= (c.117C>T)?

NPHP4 p.Asp39= (c.117C>T) is associated with nephronophthisis, nephronophthisis 4, Senior-Loken syndrome 4 (ClinVar).

How common is NPHP4 p.Asp39= (c.117C>T) in the general population?

NPHP4 p.Asp39= (c.117C>T) is ultra-rare (popmax 0.0867%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP4 p.Asp39=

c.117C>T · rs368118106 · VCV701415

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, afr)

Conditions

nephronophthisis

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 -14	GERP -4.2
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0867% African / African-American · 65/75,000 alleles

Filtering AF 0.0697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0636%

Overall 0.0271% 437/1,613,788 alleles · ultra-rare exomes 384/1,461,554 · genomes 53/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0867%	1,154
Remaining individualsnot grpmax-eligible	0.0304%	3,288
European (non-Finnish)	0.0287%	3,480
Middle Eastern	0.0165%	6,062
Admixed American	0.00667%	15,003
Finnishnot grpmax-eligible	0.00625%	15,991
South Asian	0.00439%	22,763
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Asp39=
Coding: c.117C>T
MANE Select: NM_015102
dbSNP: rs368118106
Type: single nucleotide variant
Location: chr1:5986173 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 4 Senior-Loken syndrome 4

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP4 p.Asp39Asn Uncertain significance ★ ⚠ same residue
NPHP4 p.Asp39Glu Uncertain significance ★ ⚠ same residue
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

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-asp39 (accessed [today's date]).

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