THOC2 p.Ala785=
c.2355A>G · rs368394995 · VCV3052347
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0461%, mid)
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 3.5 | GERP 0.47, phastCons 1 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0461%
Middle Eastern · 2/4,341 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0168%
Overall
0.0159%
192/1,204,106 alleles · ultra-rare
exomes 173/1,092,313 · genomes 19/111,793 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0461% | 2,171 |
| European (non-Finnish) | 0.0202% | 4,960 |
| Remaining individualsnot grpmax-eligible | 0.0169% | 5,929 |
| Admixed American | 0.00224% | 44,736 |
| South Asian | 0.00181% | 55,226 |
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
- THOC2
- Protein
- p.Ala785=
- Coding
- c.2355A>G
- MANE Select
- NM_001081550
- dbSNP
- rs368394995
- Type
- single nucleotide variant
- Location
- chrX:123631814 (GRCh38)
- Structure
- AlphaFold pLDDT 72.83 · 4 PDB
- Residue 785
- an α-helix; the 'stern domain' region
Similar variants
- THOC2 p.Cys615Tyr Likely pathogenic ★★ same type
- THOC2 p.Thr696Ile Pathogenic/Likely pathogenic ★★ same type
- THOC2 p.Ala912Pro Uncertain significance ★★ ⚠ same type
- THOC2 p.Arg1307Trp Uncertain significance ★★ ⚠ same type
- THOC2 p.Arg1468Lys Uncertain significance ★★ ⚠ same type
- THOC2 p.Asn208Ser Uncertain significance ★★ ⚠ same type
- THOC2 p.Asn414Tyr Uncertain significance ★★ ⚠ same type
- THOC2 p.Asn666Ser 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/thoc2-p-ala785 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown