THBD p.Leu12=
c.36G>A · rs777008219 · VCV1166471
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.173%, 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 -1.3 | GERP -3.5 |
| Overall | ||
| CADD | 2.571 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.173%
African / African-American · 126/72,630 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.139%
Overall
0.0086%
133/1,546,068 alleles · rare
exomes 54/1,393,750 · genomes 79/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.173% | 576 |
| Middle Eastern | 0.0168% | 5,958 |
| Admixed American | 0.00583% | 17,146 |
| Remaining individualsnot grpmax-eligible | 0.00501% | 19,959 |
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.Leu12=
- Coding
- c.36G>A
- MANE Select
- NM_000361
- dbSNP
- rs777008219
- Type
- single nucleotide variant
- Location
- chr20:23049469 (GRCh38)
- Gene constraint
- LOEUF 1.938 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 13 PDB
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-leu12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown