Is FIG4 p.Ser11= (c.33G>C) pathogenic?

FIG4 p.Ser11= (c.33G>C) is classified Conflicting classifications of pathogenicity in FIG4 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0124%, amr); Associated with Inborn genetic diseases.

What condition is associated with FIG4 p.Ser11= (c.33G>C)?

FIG4 p.Ser11= (c.33G>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4J, amyotrophic lateral sclerosis type 11 (ClinVar).

How common is FIG4 p.Ser11= (c.33G>C) in the general population?

FIG4 p.Ser11= (c.33G>C) is ultra-rare (popmax 0.0124%, amr) (gnomAD).

FIG4 p.Ser11=

c.33G>C · rs527523781 · VCV389842

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, amr)

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 -1.8	GERP -4.8
Overall
CADD	8.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0124% Admixed American · 7/56,500 alleles

Filtering AF 0.00573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0041%

Overall 0.0041% 65/1,587,112 alleles · ultra-rare exomes 59/1,434,966 · genomes 6/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0124%	8,071
European (non-Finnish)	0.0048%	20,831
Remaining individualsnot grpmax-eligible	0.00163%	61,380
African / African-American	0.00134%	74,410

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.Ser11=
Coding: c.33G>C
MANE Select: NM_014845
dbSNP: rs527523781
Type: single nucleotide variant
Location: chr6:109691468 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4J amyotrophic lateral sclerosis type 11 Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease type 4

Similar variants

FIG4 p.Ser11Ala 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.2376+2T>G Likely pathogenic ★★ same condition
FIG4 c.2459+1G>A Pathogenic ★★ same condition
FIG4 c.877-2A>C 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-ser11 (accessed [today's date]).

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