Is INF2 p.Leu69Pro (c.206T>C) pathogenic?

INF2 p.Leu69Pro (c.206T>C) is classified Likely pathogenic in INF2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-26). AlphaMissense: likely pathogenic (0.994); No allele count reported in gnomAD v4.1 (AN 1,608,514); Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Leu69Pro (c.206T>C) in the general population?

INF2 p.Leu69Pro (c.206T>C) is no allele count reported in gnomAD v4.1 (AN 1,608,514) (gnomAD).

What do computational predictors say about INF2 p.Leu69Pro (c.206T>C)?

AlphaMissense predicts likely pathogenic (score 0.994) — an in-silico prediction, not a clinical call.

INF2 p.Leu69Pro

Q: What condition is associated with INF2 p.Leu69Pro (c.206T>C)?

INF2 p.Leu69Pro (c.206T>C) is associated with Charcot-Marie-Tooth disease dominant intermediate E, Charcot-Marie-Tooth disease (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.206T>C · rs1595163820 · VCV637710

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.994 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,514)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease dominant intermediate E

Computational evidence

Protein change
AlphaMissense	0.994	likely pathogenic ✓ concordant with ClinVar · top 1% in INF2
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -16.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 7.3, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,444 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,608,514). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INF2
Protein: p.Leu69Pro
Coding: c.206T>C
MANE Select: NM_022489
dbSNP: rs1595163820
Type: single nucleotide variant
Location: chr14:104701571 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 69: the gbd/fh3 domain; a UniProt-annotated variant site (in cmtdie)

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: Charcot-Marie-Tooth disease

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

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

Similar variants

INF2 p.Leu69= Likely benign ★ same residue
INF2 p.Leu69_Ser72del 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-leu69pro (accessed [today's date]).

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