Is INVS p.Arg925= (c.2775C>T) pathogenic?

INVS p.Arg925= (c.2775C>T) is classified Conflicting classifications of pathogenicity in INVS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.203%, afr); Associated with nephronophthisis.

What condition is associated with INVS p.Arg925= (c.2775C>T)?

INVS p.Arg925= (c.2775C>T) is associated with nephronophthisis (ClinVar).

How common is INVS p.Arg925= (c.2775C>T) in the general population?

INVS p.Arg925= (c.2775C>T) is rare (popmax 0.203%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

INVS p.Arg925=

c.2775C>T · rs146360442 · VCV95598

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.203%, afr)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.46	phastCons 0.01
Overall
CADD	6.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.203% African / African-American · 152/75,048 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.0233% 376/1,613,696 alleles · rare exomes 271/1,461,376 · genomes 105/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.203%	494
Middle Eastern	0.035%	2,861
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Admixed American	0.0217%	4,617
European (non-Finnish)	0.0157%	6,378
South Asian	0.00769%	13,008
East Asian	0.00223%	44,882

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.Arg925=
Coding: c.2775C>T
MANE Select: NM_014425
dbSNP: rs146360442
Type: single nucleotide variant
Location: chr9:100293032 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.76
Residue 925: the iq 2 domain

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.Arg925His Uncertain significance ★★ ⚠ same residue
INVS p.Arg925Cys Uncertain significance ★ ⚠ same residue
INVS c.107-1G>A Likely pathogenic ★★ same condition
INVS c.1078+1G>A Pathogenic ★★ same condition
INVS c.1464+1G>T Pathogenic/Likely pathogenic ★★ same condition
INVS c.2068+2T>C Likely pathogenic ★★ same condition
INVS c.2069-1G>T Likely pathogenic ★★ same condition
INVS c.2786+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/invs-p-arg925 (accessed [today's date]).

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