Is FIG4 p.Ala5= (c.15C>T) pathogenic?

FIG4 p.Ala5= (c.15C>T) is classified Likely benign in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-03). Ultra-rare (popmax 0.0175%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with FIG4 p.Ala5= (c.15C>T)?

FIG4 p.Ala5= (c.15C>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Ala5= (c.15C>T) in the general population?

FIG4 p.Ala5= (c.15C>T) is ultra-rare (popmax 0.0175%, afr) (gnomAD).

FIG4 p.Ala5=

c.15C>T · rs917052197 · VCV1667752

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, afr)

Conditions

Charcot-Marie-Tooth disease type 4

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 -2.6	GERP -4.8
Overall
CADD	7.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% African / African-American · 13/74,276 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00819%

Overall 0.000884% 14/1,583,926 alleles · ultra-rare exomes 8/1,431,812 · genomes 6/152,114 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0175%	5,714
Remaining individualsnot grpmax-eligible	0.00163%	61,224

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.Ala5=
Coding: c.15C>T
MANE Select: NM_014845
dbSNP: rs917052197
Type: single nucleotide variant
Location: chr6:109691450 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB

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.Ala5Val 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-ala5 (accessed [today's date]).

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