Is INF2 p.Pro472fs (c.1415del) pathogenic?

INF2 p.Pro472fs (c.1415del) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Very rare (popmax 0.00394%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Pro472fs (c.1415del)?

INF2 p.Pro472fs (c.1415del) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Pro472fs (c.1415del) in the general population?

INF2 p.Pro472fs (c.1415del) is very rare (popmax 0.00394%, nfe) (gnomAD).

INF2 p.Pro472fs

c.1415del · rs2140669082 · VCV1418310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00394%, nfe)

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.1	GERP -0.13

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00394% European (non-Finnish) · 25/634,752 alleles

Filtering AF 0.0027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00336% 32/953,104 alleles · very rare exomes 32/814,394 · genomes 0/138,710 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00394%	25,390
South Asian	0.00291%	34,338
East Asian	0.00274%	36,448
Remaining individualsnot grpmax-eligible	0.0025%	39,986
Finnishnot grpmax-eligible	0.00231%	43,214
Admixed American	0.00215%	46,478
African / African-American	0.00175%	57,012

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.Pro472fs
Coding: c.1415del
MANE Select: NM_022489
dbSNP: rs2140669082
Type: Deletion
Location: chr14:104707676 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 472: 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.Pro472Gln Uncertain significance ★ ⚠ same residue
INF2 p.Pro472Thr Uncertain significance ★ ⚠ same residue
INF2 p.Ala164_Asp166del Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Leu406_Ser409del Uncertain significance ★★ same condition
INF2 p.Lys1243fs Uncertain significance ★★ same condition
INF2 p.Pro459_Pro462del Uncertain significance ★★ same condition
INF2 p.Ser1215fs Uncertain significance ★★ same condition
INF2 p.Thr1242fs Uncertain significance ★★ 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-pro472fs (accessed [today's date]).

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