Is INF2 p.Pro460Arg (c.1379C>G) pathogenic?

INF2 p.Pro460Arg (c.1379C>G) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: likely benign (0.1591); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Pro460Arg (c.1379C>G) in the general population?

INF2 p.Pro460Arg (c.1379C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INF2 p.Pro460Arg (c.1379C>G)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

INF2 p.Pro460Arg

Q: What condition is associated with INF2 p.Pro460Arg (c.1379C>G)?

INF2 p.Pro460Arg (c.1379C>G) is associated with Charcot-Marie-Tooth disease dominant intermediate E, focal segmental glomerulosclerosis 5 (ClinVar).

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type E inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.1379C>G · rs2541919942 · VCV2952885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Charcot-Marie-Tooth disease dominant intermediate E

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -10.92	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 3.7, phastCons 0.13
Regional constraint	o/e 1.23	unconstrained · MANE · 929 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	14.81	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INF2
Protein: p.Pro460Arg
Coding: c.1379C>G
MANE Select: NM_022489
dbSNP: rs2541919942
Type: single nucleotide variant
Location: chr14:104707646 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 460: the 'disordered' region

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

Disease context

Charcot-Marie-Tooth disease dominant intermediate E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 5

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type E (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: No data available

Similar variants

INF2 p.Pro460His Uncertain significance ★ ⚠ same residue
INF2 p.Pro460Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Pro460= Likely benign ★ 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

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-pro460arg (accessed [today's date]).

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