Is INF2 p.Pro445= (c.1335C>G) pathogenic?

INF2 p.Pro445= (c.1335C>G) is classified Likely benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-21). Very rare (popmax 0.00572%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Pro445= (c.1335C>G)?

INF2 p.Pro445= (c.1335C>G) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Pro445= (c.1335C>G) in the general population?

INF2 p.Pro445= (c.1335C>G) is very rare (popmax 0.00572%, nfe) (gnomAD).

INF2 p.Pro445=

c.1335C>G · rs1306481005 · VCV1136047

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00572%, nfe)

Conditions

focal segmental glomerulosclerosis 5

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 -0.12	GERP -4.7, phastCons 0.001
Overall
CADD	1.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00572% European (non-Finnish) · 48/838,956 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00392%

Overall 0.00445% 52/1,168,154 alleles · very rare exomes 50/1,035,286 · genomes 2/132,868 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00572%	17,478
African / African-American	0.00505%	19,795
Remaining individualsnot grpmax-eligible	0.00216%	46,356

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: INF2
Protein: p.Pro445=
Coding: c.1335C>G
MANE Select: NM_022489
dbSNP: rs1306481005
Type: single nucleotide variant
Location: chr14:104707602 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 445: the 'disordered' region

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

focal segmental glomerulosclerosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease dominant intermediate E

Similar variants

INF2 p.Pro445_Leu446insProPro Uncertain significance ★ same residue
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Asn202Asp 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/inf2-p-pro445 (accessed [today's date]).

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