THBD p.His565=
c.1695C>T · VCV3697169
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00346%, 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 -4.9 | GERP -3.1 |
| Overall | ||
| CADD | 0.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00346%
Admixed American · 2/57,772 alleles
Filtering AF
0.000574%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000215%
Overall
0.00025%
4/1,596,912 alleles · very rare
exomes 3/1,444,650 · genomes 1/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00346% | 28,886 |
| European (non-Finnish) | 0.000171% | 586,215 |
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.His565=
- Coding
- c.1695C>T
- MANE Select
- NM_000361
- Type
- single nucleotide variant
- Location
- chr20:23047810 (GRCh38)
- Gene constraint
- LOEUF 1.938 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 79.35 · 13 PDB
Similar variants
- THBD p.His565Arg Uncertain significance ★ ⚠ same residue
- THBD p.His565Gln Likely benign ★ 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-his565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown