Is INVS p.Cys1007del (c.3017GTT[1]) pathogenic?

INVS p.Cys1007del (c.3017GTT[1]) is classified Uncertain significance in INVS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). Very rare (popmax 8.47e-05%, nfe); Associated with nephronophthisis.

What condition is associated with INVS p.Cys1007del (c.3017GTT[1])?

INVS p.Cys1007del (c.3017GTT[1]) is associated with nephronophthisis (ClinVar).

How common is INVS p.Cys1007del (c.3017GTT[1]) in the general population?

INVS p.Cys1007del (c.3017GTT[1]) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

INVS p.Cys1007del

c.3017GTT[1] · rs2490137655 · VCV2022666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 11	phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,998 alleles

Overall 6.2e-05% 1/1,614,142 alleles · very rare exomes 1/1,461,838 · genomes 0/152,304 · 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.Cys1007del
Coding: c.3017GTT[1]
MANE Select: NM_014425
dbSNP: rs2490137655
Type: Microsatellite
Location: chr9:100297936 (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.Pro1065fs Uncertain significance ★★ same condition
INVS p.Glu114fs Pathogenic ★ same condition
INVS p.Glu598fs Pathogenic ★ same condition
INVS p.Glu906fs Pathogenic ★ same condition
INVS p.Leu101fs Pathogenic ★ same condition
INVS p.Leu225fs Pathogenic ★ same condition
INVS p.Pro292fs Pathogenic ★ same condition
INVS p.Tyr525fs 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/invs-p-cys1007del (accessed [today's date]).

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