Is FIG4 p.Cys306= (c.918C>T) pathogenic?

FIG4 p.Cys306= (c.918C>T) is classified Likely benign in FIG4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-03). Ultra-rare (popmax 0.029%, eas); Associated with Charcot-Marie-Tooth disease.

What condition is associated with FIG4 p.Cys306= (c.918C>T)?

FIG4 p.Cys306= (c.918C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Cys306= (c.918C>T) in the general population?

FIG4 p.Cys306= (c.918C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

FIG4 p.Cys306=

c.918C>T · rs369159531 · VCV543511

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.5	GERP -4.2
Overall
CADD	0.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,802 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00397% 64/1,612,666 alleles · ultra-rare exomes 53/1,460,586 · genomes 11/152,080 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,446
African / African-American	0.00534%	18,710
Remaining individualsnot grpmax-eligible	0.00481%	20,801
European (non-Finnish)	0.00339%	29,479
Finnishnot grpmax-eligible	0.00313%	32,000
Admixed American	0.00167%	59,894
South Asian	0.0011%	91,052

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.Cys306=
Coding: c.918C>T
MANE Select: NM_014845
dbSNP: rs369159531
Type: single nucleotide variant
Location: chr6:109743151 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 306: the sac domain

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 4

Similar variants

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
FIG4 p.Arg183Ter 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-cys306 (accessed [today's date]).

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