Is NPHP4 p.Met1075Trp (c.3223_3224delinsTG) pathogenic?

NPHP4 p.Met1075Trp (c.32233224delinsTG) is classified Uncertain significance in NPHP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-09). No gnomAD frequency available for this variant; Associated with nephronophthisis.

What condition is associated with NPHP4 p.Met1075Trp (c.3223_3224delinsTG)?

NPHP4 p.Met1075Trp (c.3223_3224delinsTG) is associated with nephronophthisis (ClinVar).

How common is NPHP4 p.Met1075Trp (c.3223_3224delinsTG) in the general population?

NPHP4 p.Met1075Trp (c.3223_3224delinsTG) is no gnomAD frequency available for this variant (gnomAD).

How is Nephronophthisis inherited?

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

NPHP4 p.Met1075Trp

c.3223_3224delinsTG · rs2523113287 · VCV2097950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.1	GERP -2.6
Regional constraint	o/e 1.02	unconstrained · MANE · 123 kb · p 0.49 · regional, not allelic
Region caveats
Repeat context	tandem	(CCTGCA)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHP4
Protein: p.Met1075Trp
Coding: c.3223_3224delinsTG
MANE Select: NM_015102
dbSNP: rs2523113287
Type: Indel
Location: chr1:5874478 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 1075: the 'sufficient for basal bodies localization' region

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

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP4 p.Lys474fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Gln748Lys Uncertain significance ★★ same condition
NPHP4 p.Gly929Arg Uncertain significance ★ same condition
NPHP4 p.Val291_Phe297delinsLeu Uncertain significance ★ same condition
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

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-met1075trp (accessed [today's date]).

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