TCHH p.Arg863=
c.2587A>C · VCV4911155
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00492%, nfe)
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 -0.41 | GERP -2.4 |
| Overall | ||
| CADD | 5.188 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00492%
European (non-Finnish) · 58/1,179,836 alleles
Filtering AF
0.00386%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00353%
Overall
0.00384%
62/1,613,222 alleles · very rare
exomes 57/1,461,838 · genomes 5/151,384 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00492% | 20,342 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| African / African-American | 0.00134% | 74,642 |
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
- TCHH
- Protein
- p.Arg863=
- Coding
- c.2587A>C
- MANE Select
- NM_007113
- Type
- single nucleotide variant
- Location
- chr1:152110630 (GRCh38)
- Gene constraint
- LOEUF 1.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.96
- Residue 863
- the 'disordered' region
Similar variants
- TCHH p.Glu626Gly Uncertain significance ★★ ⚠ same type
- TCHH p.Ala686Gly Benign ★★ same type
- TCHH p.Arg1444Pro Likely benign ★★ ⚠ same type
- TCHH p.Arg1876Gln Likely benign ★★ same type
- TCHH p.Arg629= Benign/Likely benign ★★ same type
- TCHH p.Glu1601= Benign/Likely benign ★★ same type
- TCHH p.Glu430Gln Benign ★★ same type
- TCHH p.Glu650Lys Likely benign ★★ 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/tchh-p-arg863 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown