Is NPHP1 p.Pro272fs (c.812_813insA) pathogenic?

NPHP1 p.Pro272fs (c.812813insA) is classified Pathogenic in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-26). No gnomAD frequency available for this variant; Associated with nephronophthisis.

What condition is associated with NPHP1 p.Pro272fs (c.812_813insA)?

NPHP1 p.Pro272fs (c.812_813insA) is associated with nephronophthisis (ClinVar).

How common is NPHP1 p.Pro272fs (c.812_813insA) in the general population?

NPHP1 p.Pro272fs (c.812_813insA) 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.

NPHP1 p.Pro272fs

c.812_813insA · rs2104553788 · VCV1415124

Pathogenic Single submitter

Classification

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

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 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.95	GERP -3.4, phastCons 0.99

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.Pro272fs
Coding: c.812_813insA
MANE Select: NM_001128178
dbSNP: rs2104553788
Type: Insertion
Location: chr2:110163094 (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

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP1 c.771+185_771+186insA Likely benign ★ same condition
NPHP1 c.771+187_771+188insG Likely benign ★ same condition
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.141_143+40del 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-pro272fs (accessed [today's date]).

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