Is FIG4 p.Ile372= (c.1116C>T) pathogenic?

FIG4 p.Ile372= (c.1116C>T) is classified Likely benign in FIG4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-07). Ultra-rare (popmax 0.0117%, amr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with FIG4 p.Ile372= (c.1116C>T)?

FIG4 p.Ile372= (c.1116C>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Ile372= (c.1116C>T) in the general population?

FIG4 p.Ile372= (c.1116C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

FIG4 p.Ile372=

c.1116C>T · rs754932535 · VCV1622067

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.81	GERP 0.19, phastCons 1
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,896 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000434% 7/1,612,174 alleles · ultra-rare exomes 6/1,460,036 · genomes 1/152,138 · 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: FIG4
Protein: p.Ile372=
Coding: c.1116C>T
MANE Select: NM_014845
dbSNP: rs754932535
Type: single nucleotide variant
Location: chr6:109743751 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 372: the sac domain

Full FIG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FIG4 p.Ile372Met Uncertain significance ★ ⚠ same residue
FIG4 c.1040-1G>A Likely pathogenic ★★ same condition
FIG4 c.1584-1G>T Likely pathogenic ★★ same condition
FIG4 c.1948+1G>A Likely pathogenic ★★ same condition
FIG4 c.1949-10T>G Pathogenic/Likely pathogenic ★★ same condition
FIG4 c.2459+1G>A Pathogenic ★★ same condition
FIG4 c.877-2A>C Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Arg152Ter 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/fig4-p-ile372 (accessed [today's date]).

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