THBD p.Ser482=
c.1446C>T · rs774549921 · VCV1926587
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0066%, sas)
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 0.76 | GERP -2.8 |
| Overall | ||
| CADD | 4.661 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0066%
South Asian · 6/90,968 alleles
Filtering AF
0.00287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00124%
20/1,612,584 alleles · very rare
exomes 18/1,460,336 · genomes 2/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0066% | 15,161 |
| Admixed American | 0.00334% | 29,948 |
| African / African-American | 0.00267% | 37,466 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,390 |
| European (non-Finnish) | 0.000763% | 131,062 |
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.Ser482=
- Coding
- c.1446C>T
- MANE Select
- NM_000361
- dbSNP
- rs774549921
- Type
- single nucleotide variant
- Location
- chr20:23048059 (GRCh38)
- Gene constraint
- LOEUF 1.938 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 13 PDB
- Residue 482
- 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-ser482 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown