Is TFG p.Arg113= (c.337C>A) pathogenic?

TFG p.Arg113= (c.337C>A) is classified Likely benign in TFG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). Very rare (popmax 0.00398%, nfe); Associated with hereditary motor and sensory neuropathy, Okinawa type.

How common is TFG p.Arg113= (c.337C>A) in the general population?

TFG p.Arg113= (c.337C>A) is very rare (popmax 0.00398%, nfe) (gnomAD).

TFG p.Arg113=

Q: What condition is associated with TFG p.Arg113= (c.337C>A)?

TFG p.Arg113= (c.337C>A) is associated with hereditary motor and sensory neuropathy, Okinawa type, hereditary spastic paraplegia 57 (ClinVar).

Q: How is Hereditary motor and sensory neuropathy, Okinawa type inherited?

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

c.337C>A · rs764959531 · VCV1605342

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Conditions

hereditary motor and sensory neuropathy, Okinawa type

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 0.51	GERP 0.72, phastCons 1
Overall
CADD	11.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00398% European (non-Finnish) · 47/1,179,452 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00298% 48/1,612,832 alleles · very rare exomes 44/1,460,752 · genomes 4/152,080 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,095
Remaining individualsnot grpmax-eligible	0.0016%	62,436

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: TFG
Protein: p.Arg113=
Coding: c.337C>A
MANE Select: NM_006070
dbSNP: rs764959531
Type: single nucleotide variant
Location: chr3:100728780 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 60.51 · 3 PDB

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

Disease context

hereditary motor and sensory neuropathy, Okinawa type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 57

For Hereditary motor and sensory neuropathy, Okinawa type (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

TFG p.Arg113Leu Uncertain significance ★ ⚠ same residue
TFG p.Arg113Ter Likely pathogenic ★ same residue
TFG p.Arg106Cys Pathogenic ★★ same condition
TFG p.Arg22Trp Pathogenic ★★ same condition
TFG p.Pro285Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
TFG c.820+3G>A Uncertain significance ★★ same condition
TFG p.Ala184Thr Uncertain significance ★★ ⚠ same condition
TFG p.Ala326Ser 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/tfg-p-arg113 (accessed [today's date]).

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