Is INF2 p.Pro1030= (c.3090C>T) pathogenic?

INF2 p.Pro1030= (c.3090C>T) is classified Likely benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Very rare (popmax 0.00229%, eas); Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Pro1030= (c.3090C>T) in the general population?

INF2 p.Pro1030= (c.3090C>T) is very rare (popmax 0.00229%, eas) (gnomAD).

INF2 p.Pro1030=

Q: What condition is associated with INF2 p.Pro1030= (c.3090C>T)?

INF2 p.Pro1030= (c.3090C>T) 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.3090C>T · rs1306938117 · VCV1608785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00229%, eas)

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 -7	GERP -2.1
Overall
CADD	1.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% East Asian · 1/43,604 alleles

Filtering AF 0.000294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000213%

Overall 0.00063% 10/1,588,214 alleles · very rare exomes 9/1,436,014 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00229%	43,604
Remaining individualsnot grpmax-eligible	0.00163%	61,520
European (non-Finnish)	0.000684%	146,141

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.Pro1030=
Coding: c.3090C>T
MANE Select: NM_022489
dbSNP: rs1306938117
Type: single nucleotide variant
Location: chr14:104714252 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1030: 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.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
INF2 p.Glu184Lys 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-pro1030 (accessed [today's date]).

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