Is TFG p.Pro96= (c.288C>G) pathogenic?

TFG p.Pro96= (c.288C>G) is classified Likely benign in TFG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). Very rare (popmax 0.00269%, afr); Associated with hereditary motor and sensory neuropathy, Okinawa type.

How common is TFG p.Pro96= (c.288C>G) in the general population?

TFG p.Pro96= (c.288C>G) is very rare (popmax 0.00269%, afr) (gnomAD).

TFG p.Pro96=

Q: What condition is associated with TFG p.Pro96= (c.288C>G)?

TFG p.Pro96= (c.288C>G) 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.288C>G · rs1180461235 · VCV706148

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

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 -0.43	GERP 0.81, phastCons 0.072
Overall
CADD	8.557	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,398 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00186% 27/1,454,120 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,199
European (non-Finnish)	0.00204%	49,023
Remaining individualsnot grpmax-eligible	0.00161%	62,136

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.Pro96=
Coding: c.288C>G
MANE Select: NM_006070
dbSNP: rs1180461235
Type: single nucleotide variant
Location: chr3:100728731 (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.Pro96Ser Uncertain significance ★ ⚠ 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
TFG p.Ala382Val 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-pro96 (accessed [today's date]).

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