THBD p.Ala509=
c.1527C>A · rs369357178 · VCV1012477
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0157%, 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 -5.7 | GERP -3.4 |
| Overall | ||
| CADD | 0.101 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0157%
East Asian · 7/44,658 alleles
Filtering AF
0.00729%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00517%
Overall
0.000932%
15/1,608,734 alleles · ultra-rare
exomes 10/1,456,362 · genomes 5/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0157% | 6,380 |
| South Asian | 0.00775% | 12,910 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,266 |
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
- THBD
- Protein
- p.Ala509=
- Coding
- c.1527C>A
- MANE Select
- NM_000361
- dbSNP
- rs369357178
- Type
- single nucleotide variant
- Location
- chr20:23047978 (GRCh38)
- Gene constraint
- LOEUF 1.938 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 13 PDB
- Residue 509
- the 'involved in alpha-l/beta-2 and alpha-m/beta-2 integrin binding' region
Similar variants
- THBD p.Cys537Ter Pathogenic/Likely pathogenic ★★ same type
- THBD p.Ala139Ser Uncertain significance ★★ ⚠ same type
- THBD p.Ala21Ser Uncertain significance ★★ ⚠ same type
- THBD p.Ala255Pro Uncertain significance ★★ ⚠ same type
- THBD p.Ala271Thr Uncertain significance ★★ ⚠ same type
- THBD p.Ala272Val Uncertain significance ★★ ⚠ same type
- THBD p.Ala284Gly Uncertain significance ★★ ⚠ same type
- THBD p.Ala395Val 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/thbd-p-ala509 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown