THBD p.Asp486=
c.1458C>T · rs200575906 · VCV1157508
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0746%, afr)
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 -8.7 | GERP -2.1 |
| Overall | ||
| CADD | 0.363 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0746%
African / African-American · 56/75,042 alleles
Filtering AF
0.0589%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0533%
Overall
0.00372%
60/1,612,140 alleles · ultra-rare
exomes 27/1,459,786 · genomes 33/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0746% | 1,340 |
| Admixed American | 0.00334% | 29,927 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,384 |
| European (non-Finnish) | 8.48e-05% | 1,179,318 |
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.Asp486=
- Coding
- c.1458C>T
- MANE Select
- NM_000361
- dbSNP
- rs200575906
- Type
- single nucleotide variant
- Location
- chr20:23048047 (GRCh38)
- Gene constraint
- LOEUF 1.938 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 13 PDB
- Residue 486
- the 'involved in alpha-l/beta-2 and alpha-m/beta-2 integrin binding' region; the 'disordered' region; a UniProt-annotated variant site (in thph12 and ahus6; cells transfected with the mutant are less effective in converting c3b to ic3b on the cell surface after complement activation)
Similar variants
- THBD p.Asp486Tyr Benign/Likely benign ★★ same residue
- THBD p.Asp486Glu Uncertain significance ★ ⚠ same residue
- 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
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-asp486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown