Is FIG4 p.Arg820Ser (c.2460A>C) pathogenic?

FIG4 p.Arg820Ser (c.2460A>C) is classified Uncertain significance in FIG4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-20). AlphaMissense: likely pathogenic (0.6318); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 4J.

What condition is associated with FIG4 p.Arg820Ser (c.2460A>C)?

FIG4 p.Arg820Ser (c.2460A>C) is associated with Charcot-Marie-Tooth disease type 4J, amyotrophic lateral sclerosis type 11 (ClinVar).

How common is FIG4 p.Arg820Ser (c.2460A>C) in the general population?

FIG4 p.Arg820Ser (c.2460A>C) is absent from gnomAD v4.1 (gnomAD).

How is Charcot-Marie-Tooth disease type 4J inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FIG4 p.Arg820Ser (c.2460A>C)?

AlphaMissense predicts likely pathogenic (score 0.6318) — an in-silico prediction, not a clinical call.

FIG4 p.Arg820Ser

c.2460A>C · rs886060984 · VCV355045

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6318 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4J

Computational evidence

Protein change
AlphaMissense	0.6318	likely pathogenic
REVEL	0.287	benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.31	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -4, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	15.04	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg820Ser
Coding: c.2460A>C
MANE Select: NM_014845
dbSNP: rs886060984
Type: single nucleotide variant
Location: chr6:109796765 (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

Charcot-Marie-Tooth disease type 4J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 11

For Charcot-Marie-Tooth disease type 4J (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Childhood, Infancy

Similar variants

FIG4 p.Arg820Ile Uncertain significance ★ same residue
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
FIG4 p.Arg88Ter 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-arg820ser (accessed [today's date]).

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