TFE3 p.Ala138=
c.414C>T · rs372564649 · VCV2660506
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0179%, eas)
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 -0.26 | GERP -3.5, phastCons 0.56 |
| Overall | ||
| CADD | 2.114 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0179%
East Asian · 6/33,535 alleles
Filtering AF
0.0077%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0053%
Overall
0.00639%
77/1,204,706 alleles · ultra-rare
exomes 69/1,093,632 · genomes 8/111,074 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0179% | 5,589 |
| Remaining individualsnot grpmax-eligible | 0.0169% | 5,914 |
| South Asian | 0.0143% | 7,007 |
| European (non-Finnish) | 0.00616% | 16,233 |
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
- TFE3
- Protein
- p.Ala138=
- Coding
- c.414C>T
- MANE Select
- NM_006521
- dbSNP
- rs372564649
- Type
- single nucleotide variant
- Location
- chrX:49039227 (GRCh38)
- Structure
- AlphaFold pLDDT 60.54 · 1 PDB
- Residue 138
- the 'disordered' region
Similar variants
- TFE3 p.Arg117Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- TFE3 p.Thr187Met Pathogenic/Likely pathogenic ★★ same type
- TFE3 p.Gly370Ser Uncertain significance ★★ ⚠ same type
- TFE3 p.His509Asn Uncertain significance ★★ ⚠ same type
- TFE3 p.Pro495Ser Uncertain significance ★★ ⚠ same type
- TFE3 p.Ser153Pro Uncertain significance ★★ ⚠ same type
- TFE3 p.Ser377Asn Uncertain significance ★★ ⚠ same type
- TFE3 p.Val311Met Uncertain significance ★★ ⚠ same type
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/tfe3-p-ala138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown