Is TFG p.Val116= (c.348G>C) pathogenic?

TFG p.Val116= (c.348G>C) is classified Likely benign in TFG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-06). Absent from gnomAD v4.1; Associated with hereditary motor and sensory neuropathy, Okinawa type.

How common is TFG p.Val116= (c.348G>C) in the general population?

TFG p.Val116= (c.348G>C) is absent from gnomAD v4.1 (gnomAD).

TFG p.Val116=

Q: What condition is associated with TFG p.Val116= (c.348G>C)?

TFG p.Val116= (c.348G>C) 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.348G>C · rs1576366448 · VCV794684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.4	GERP -1.6, phastCons 0.98
Overall
CADD	6.321	PHRED · no single calibrated threshold — expert panels disagree

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: TFG
Protein: p.Val116=
Coding: c.348G>C
MANE Select: NM_006070
dbSNP: rs1576366448
Type: single nucleotide variant
Location: chr3:100728791 (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.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
TFG p.Ala382Val Uncertain significance ★★ ⚠ same condition
TFG p.Arg107Gln 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-val116 (accessed [today's date]).

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