Is FIG4 p.Leu209= (c.627A>G) pathogenic?

FIG4 p.Leu209= (c.627A>G) is classified Benign/Likely benign in FIG4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-17). Rare (popmax 0.384%, afr); Associated with Inborn genetic diseases.

What condition is associated with FIG4 p.Leu209= (c.627A>G)?

FIG4 p.Leu209= (c.627A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Leu209= (c.627A>G) in the general population?

FIG4 p.Leu209= (c.627A>G) is rare (popmax 0.384%, afr) (gnomAD).

FIG4 p.Leu209=

c.627A>G · rs140111406 · VCV447338

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.384%, afr)

Conditions

Inborn genetic diseases

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 1.2	GERP -4.4, phastCons 0.16
Overall
CADD	7.272	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.384% African / African-American · 288/75,002 alleles

Filtering AF 0.348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.333%

Overall 0.0219% 353/1,613,550 alleles · rare exomes 191/1,461,264 · genomes 162/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.384%	260
East Asian	0.0424%	2,361
Remaining individualsnot grpmax-eligible	0.0352%	2,839
Admixed American	0.0217%	4,614
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00156%	64,022
European (non-Finnish)	0.000593%	168,514

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.Leu209=
Coding: c.627A>G
MANE Select: NM_014845
dbSNP: rs140111406
Type: single nucleotide variant
Location: chr6:109735279 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 209: the sac domain

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

Disease context

Inborn genetic diseases — 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-leu209 (accessed [today's date]).

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