Is FIG4 p.Arg384Ter (c.1150A>T) pathogenic?

FIG4 p.Arg384Ter (c.1150A>T) is classified Likely pathogenic in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-23). Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis type 11.

What condition is associated with FIG4 p.Arg384Ter (c.1150A>T)?

FIG4 p.Arg384Ter (c.1150A>T) is associated with amyotrophic lateral sclerosis type 11, Yunis-Varon syndrome, Charcot-Marie-Tooth disease type 4J (ClinVar).

How common is FIG4 p.Arg384Ter (c.1150A>T) in the general population?

FIG4 p.Arg384Ter (c.1150A>T) is absent from gnomAD v4.1 (gnomAD).

FIG4 p.Arg384Ter

c.1150A>T · VCV3892147

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

amyotrophic lateral sclerosis type 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.1	GERP 0.86, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FIG4
Protein: p.Arg384Ter
Coding: c.1150A>T
MANE Select: NM_014845
Type: single nucleotide variant
Location: chr6:109760262 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 384: the sac domain

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

Also linked: Yunis-Varon syndrome Charcot-Marie-Tooth disease type 4J bilateral parasagittal parieto-occipital polymicrogyria

Similar variants

FIG4 p.Arg384fs Pathogenic/Likely pathogenic ★★ same residue
FIG4 c.1040-1G>A 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
FIG4 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Arg265Ter Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Arg381Ter 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-arg384ter (accessed [today's date]).

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