THOC2 p.Ser1589=
c.4767G>A · rs369296561 · VCV764241
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0221%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.30 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.61 | GERP -3.7, phastCons 0.013 |
| Overall | ||
| CADD | 7.551 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0221%
European (non-Finnish) · 198/893,913 alleles
Filtering AF
0.0196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0186%
Overall
0.0171%
206/1,207,028 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0221% | 4,515 |
| Admixed American | 0.00663% | 15,091 |
| Remaining individualsnot grpmax-eligible | 0.00421% | 23,750 |
| African / African-American | 0.00351% | 28,485 |
| South Asian | 0.00178% | 56,255 |
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.Ser1589=
- Coding
- c.4767G>A
- MANE Select
- NM_001081550
- dbSNP
- rs369296561
- Type
- single nucleotide variant
- Location
- chrX:123610951 (GRCh38)
- Structure
- AlphaFold pLDDT 72.83 · 4 PDB
- Residue 1589
- the 'charged domain' region; the 'disordered' region
Similar variants
- THOC2 p.Ser1589Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser1589 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown