TSFM p.Asp251=
c.753C>T · rs769262352 · VCV1577823
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00517%, amr)
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 -0.58 | GERP -2.4 |
| Overall | ||
| CADD | 3.731 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00517%
Admixed American · 3/58,008 alleles
Filtering AF
0.00137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00068%
Overall
0.00118%
19/1,603,842 alleles · very rare
exomes 16/1,451,526 · genomes 3/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00517% | 19,336 |
| African / African-American | 0.00267% | 37,449 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,164 |
| South Asian | 0.00112% | 89,474 |
| European (non-Finnish) | 0.00102% | 97,922 |
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
- TSFM
- Protein
- p.Asp251=
- Coding
- c.753C>T
- MANE Select
- NM_005726
- dbSNP
- rs769262352
- Type
- single nucleotide variant
- Location
- chr12:57796358 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.87 · 1 PDB
Similar variants
- TSFM p.Asp251Asn Uncertain significance ⚠ same residue
- TSFM c.231+1G>A Likely pathogenic ★★ same type
- TSFM c.232-2A>G Likely pathogenic ★★ same type
- TSFM c.484-1G>A Likely pathogenic ★★ same type
- TSFM c.484-1G>T Likely pathogenic ★★ same type
- TSFM c.57+1G>A Likely pathogenic ★★ same type
- TSFM c.571+1G>C Pathogenic/Likely pathogenic ★★ same type
- TSFM p.Arg201Ter Pathogenic/Likely pathogenic ★★ 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/tsfm-p-asp251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown