Is INVS p.Arg899Ter (c.2695C>T) pathogenic?

INVS p.Arg899Ter (c.2695C>T) is classified Pathogenic/Likely pathogenic in INVS (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-08-26). Ultra-rare (popmax 0.0123%, nfe); Associated with INVS-related disorders.

What condition is associated with INVS p.Arg899Ter (c.2695C>T)?

INVS p.Arg899Ter (c.2695C>T) is associated with INVS-related disorders, nephronophthisis 2, nephronophthisis (ClinVar).

How common is INVS p.Arg899Ter (c.2695C>T) in the general population?

INVS p.Arg899Ter (c.2695C>T) is ultra-rare (popmax 0.0123%, nfe) (gnomAD).

INVS p.Arg899Ter

c.2695C>T · rs200844390 · VCV11962

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, nfe)

Conditions

INVS-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0123% European (non-Finnish) · 145/1,178,976 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00998%

Overall 0.00949% 153/1,612,784 alleles · ultra-rare exomes 140/1,460,652 · genomes 13/152,132 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0123%	8,131
African / African-American	0.00401%	24,962
Admixed American	0.00333%	29,994
Remaining individualsnot grpmax-eligible	0.0032%	31,217
East Asian	0.00223%	44,862

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.Arg899Ter
Coding: c.2695C>T
MANE Select: NM_014425
dbSNP: rs200844390
Type: single nucleotide variant
Location: chr9:100292952 (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

INVS-related disorders

Also linked: nephronophthisis 2 nephronophthisis

Similar variants

INVS p.Arg899Gln Uncertain significance ★ ⚠ same residue
INVS p.Arg899= Likely benign ★ 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-arg899ter (accessed [today's date]).

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