Is TARDBP p.Phe367= (c.1101C>T) pathogenic?

TARDBP p.Phe367= (c.1101C>T) is classified Likely benign in TARDBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-03). Ultra-rare (popmax 0.0107%, afr); Associated with FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED.

How common is TARDBP p.Phe367= (c.1101C>T) in the general population?

TARDBP p.Phe367= (c.1101C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

TARDBP p.Phe367=

Q: What condition is associated with TARDBP p.Phe367= (c.1101C>T)?

TARDBP p.Phe367= (c.1101C>T) is associated with FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED, amyotrophic lateral sclerosis type 10 (ClinVar).

c.1101C>T · rs377531374 · VCV1139307

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED

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 -0.73	GERP -2.7, phastCons 0.029
Overall
CADD	7.775	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,530 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00132% 21/1,596,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,316
South Asian	0.00112%	89,552
European (non-Finnish)	0.00103%	97,385

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: TARDBP
Protein: p.Phe367=
Coding: c.1101C>T
MANE Select: NM_007375
dbSNP: rs377531374
Type: single nucleotide variant
Location: chr1:11022510 (GRCh38)
Gene constraint: LOEUF 0.229 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.49 · 44 PDB
Residue 367: a β-strand; the 'interaction with ubqln2' region; the 'disordered' region

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

Disease context

FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 10

Similar variants

TARDBP p.Ala315Thr Pathogenic ★★ ⚠ same condition
TARDBP p.Ala382Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Asn352Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Gly287Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Gly298Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Gly348Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Ile383Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
TARDBP p.Met337Val Pathogenic/Likely 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/tardbp-p-phe367 (accessed [today's date]).

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