Is INF2 p.Arg340= (c.1018C>A) pathogenic?

INF2 p.Arg340= (c.1018C>A) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-01). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Arg340= (c.1018C>A) in the general population?

INF2 p.Arg340= (c.1018C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

INF2 p.Arg340=

Q: What condition is associated with INF2 p.Arg340= (c.1018C>A)?

INF2 p.Arg340= (c.1018C>A) 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.1018C>A · rs753651657 · VCV1902597

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Charcot-Marie-Tooth disease dominant intermediate E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 5.2, phastCons 1
Overall
CADD	12.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 11/1,608,904 alleles · ultra-rare exomes 9/1,456,876 · genomes 2/152,028 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
Admixed American	0.00168%	59,524
European (non-Finnish)	0.000764%	130,933

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.Arg340=
Coding: c.1018C>A
MANE Select: NM_022489
dbSNP: rs753651657
Type: single nucleotide variant
Location: chr14:104707285 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB

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.Arg340Gln 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-arg340 (accessed [today's date]).

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