Is FIG4 p.Val96= (c.288G>C) pathogenic?

FIG4 p.Val96= (c.288G>C) is classified Uncertain significance in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). Very rare (popmax 8.48e-05%, nfe); Associated with amyotrophic lateral sclerosis type 11.

What condition is associated with FIG4 p.Val96= (c.288G>C)?

FIG4 p.Val96= (c.288G>C) is associated with amyotrophic lateral sclerosis type 11 (ClinVar).

How common is FIG4 p.Val96= (c.288G>C) in the general population?

FIG4 p.Val96= (c.288G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

FIG4 p.Val96=

c.288G>C · VCV3896868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

amyotrophic lateral sclerosis type 11

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 -0.086	GERP -4.9, phastCons 0.012
Overall
CADD	5.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,678 alleles

Overall 6.2e-05% 1/1,613,612 alleles · very rare exomes 1/1,461,396 · genomes 0/152,216 · 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.Val96=
Coding: c.288G>C
MANE Select: NM_014845
Type: single nucleotide variant
Location: chr6:109716567 (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

amyotrophic lateral sclerosis type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FIG4 c.2376+2T>G Likely pathogenic ★★ same condition
FIG4 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Arg88Ter Pathogenic ★★ same condition
FIG4 p.Ile41Thr Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Trp246Ter Pathogenic ★★ same condition
FIG4 c.1388+5G>T Uncertain significance ★★ same condition
FIG4 c.2096+3A>G Uncertain significance ★★ same condition
FIG4 c.-132A>G Uncertain significance ★★ 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-val96 (accessed [today's date]).

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