Is INVS p.Asp404fs (c.1211del) pathogenic?

INVS p.Asp404fs (c.1211del) is classified Pathogenic in INVS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). Very rare (popmax 0.0011%, sas); Associated with nephronophthisis.

What condition is associated with INVS p.Asp404fs (c.1211del)?

INVS p.Asp404fs (c.1211del) is associated with nephronophthisis (ClinVar).

How common is INVS p.Asp404fs (c.1211del) in the general population?

INVS p.Asp404fs (c.1211del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

INVS p.Asp404fs

c.1211del · rs2490003602 · VCV2712588

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.2e-05% 1/1,613,958 alleles · very rare exomes 1/1,461,636 · genomes 0/152,322 · joint denominator

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: INVS
Protein: p.Asp404fs
Coding: c.1211del
MANE Select: NM_014425
dbSNP: rs2490003602
Type: Deletion
Location: chr9:100252415 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.76

Full INVS 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

INVS p.Asn278fs Pathogenic/Likely pathogenic ★★ same condition
INVS p.Gln485fs Pathogenic ★★ same condition
INVS p.Gln587fs Pathogenic ★★ same condition
INVS p.Gly456fs Pathogenic/Likely pathogenic ★★ same condition
INVS p.Lys834fs Pathogenic/Likely pathogenic ★★ same condition
INVS p.Ser721fs Pathogenic/Likely pathogenic ★★ same condition
INVS c.2069-18_2069-16del Benign/Likely benign ★★ same condition
INVS c.274-15_274-14del Benign ★★ 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/invs-p-asp404fs (accessed [today's date]).

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