Is NPHP1 p.Ser121fs (c.361_362dup) pathogenic?

NPHP1 p.Ser121fs (c.361362dup) is classified Likely pathogenic in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). No gnomAD frequency available for this variant; Associated with nephronophthisis 1.

What condition is associated with NPHP1 p.Ser121fs (c.361_362dup)?

NPHP1 p.Ser121fs (c.361_362dup) is associated with nephronophthisis 1 (ClinVar).

How common is NPHP1 p.Ser121fs (c.361_362dup) in the general population?

NPHP1 p.Ser121fs (c.361_362dup) is no gnomAD frequency available for this variant (gnomAD).

NPHP1 p.Ser121fs

c.361_362dup · rs2467405206 · VCV2681747

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nephronophthisis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4	GERP -2.9, phastCons 0.001
Region caveats
Repeat context	tandem	(TTCCTC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: NPHP1
Protein: p.Ser121fs
Coding: c.361_362dup
MANE Select: NM_001128178
dbSNP: rs2467405206
Type: Duplication
Location: chr2:110169965 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB
Residue 121: the 'disordered' region; a modified residue (phosphoserine; by ck2)

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP1 p.Pro186fs Pathogenic ★★ same condition
NPHP1 c.771+37_771+38dup Likely pathogenic ★ same condition
NPHP1 p.Gly161fs Pathogenic ★ same condition
NPHP1 p.Ile632fs Likely pathogenic ★ same condition
NPHP1 c.625-3dup Conflicting classifications of pathogenicity ★ 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-ser121fs (accessed [today's date]).

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