Is INF2 p.Arg9Pro (c.26G>C) pathogenic?

INF2 p.Arg9Pro (c.26G>C) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: ambiguous (0.3728); Very rare (popmax 0.000171%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Arg9Pro (c.26G>C)?

INF2 p.Arg9Pro (c.26G>C) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Arg9Pro (c.26G>C) in the general population?

INF2 p.Arg9Pro (c.26G>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about INF2 p.Arg9Pro (c.26G>C)?

AlphaMissense predicts ambiguous (score 0.3728) — an in-silico prediction, not a clinical call.

INF2 p.Arg9Pro

c.26G>C · rs529349803 · VCV1950794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
AlphaMissense	0.3728	ambiguous
REVEL	0.445	indeterminate
SaProt	LLR -10.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 5.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 99 bp · p 0.8 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,168,142 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,590,604 alleles · very rare exomes 2/1,438,238 · genomes 0/152,366 · joint denominator

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.Arg9Pro
Coding: c.26G>C
MANE Select: NM_022489
dbSNP: rs529349803
Type: single nucleotide variant
Location: chr14:104701391 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 9: the gbd/fh3 domain; the 'disordered' region; an α-helix

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.Arg9Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Arg9Ser 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

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-arg9pro (accessed [today's date]).

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