THOC2 p.Ala670=
c.2010G>A · rs1239381361 · VCV2661348
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00181%, sas)
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 -0.46 | GERP -5.3, phastCons 0.12 |
| Overall | ||
| CADD | 7.652 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00181%
South Asian · 1/55,197 alleles
Filtering AF
0.000105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.1e-05%
Overall
0.000415%
5/1,203,506 alleles · very rare
exomes 5/1,090,412 · genomes 0/113,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00181% | 55,197 |
| European (non-Finnish) | 0.000449% | 222,765 |
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.Ala670=
- Coding
- c.2010G>A
- MANE Select
- NM_001081550
- dbSNP
- rs1239381361
- Type
- single nucleotide variant
- Location
- chrX:123636087 (GRCh38)
- Structure
- AlphaFold pLDDT 72.83 · 4 PDB
- Residue 670
- the 'mif4g domain; interaction with thoc3 and ddx39b' 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-ala670 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown