Is INVS p.Pro895= (c.2685C>T) pathogenic?

INVS p.Pro895= (c.2685C>T) is classified Likely benign in INVS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0214%, nfe); Associated with Inborn genetic diseases.

What condition is associated with INVS p.Pro895= (c.2685C>T)?

INVS p.Pro895= (c.2685C>T) is associated with Inborn genetic diseases, nephronophthisis 2, nephronophthisis (ClinVar).

How common is INVS p.Pro895= (c.2685C>T) in the general population?

INVS p.Pro895= (c.2685C>T) is ultra-rare (popmax 0.0214%, nfe) (gnomAD).

INVS p.Pro895=

c.2685C>T · rs371932940 · VCV1623368

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7
Overall
CADD	7.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% European (non-Finnish) · 252/1,179,168 alleles

Filtering AF 0.0192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.0181% 292/1,613,010 alleles · ultra-rare exomes 273/1,460,870 · genomes 19/152,140 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0288%	3,469
European (non-Finnish)grpmax	0.0214%	4,679
South Asian	0.0165%	6,071
African / African-American	0.00668%	14,976
East Asian	0.00223%	44,856
Finnishnot grpmax-eligible	0.00156%	64,024

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro895=
Coding: c.2685C>T
MANE Select: NM_014425
dbSNP: rs371932940
Type: single nucleotide variant
Location: chr9:100292942 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 2 nephronophthisis

Similar variants

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
INVS c.2786+2T>C Pathogenic/Likely pathogenic ★★ same condition
INVS c.615+1G>A 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-pro895 (accessed [today's date]).

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