THOC2 p.Asp1339=
c.4017T>C · VCV3777971
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.221%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.128 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 6.629 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.221%
South Asian · 125/56,487 alleles
Filtering AF
0.19%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.178%
Overall
0.0112%
135/1,207,556 alleles · rare
exomes 129/1,097,444 · genomes 6/110,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.221% | 452 |
| Remaining individualsnot grpmax-eligible | 0.0147% | 6,793 |
| African / African-American | 0.00353% | 28,293 |
| European (non-Finnish) | 0.000112% | 894,614 |
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.Asp1339=
- Coding
- c.4017T>C
- MANE Select
- NM_001081550
- Type
- single nucleotide variant
- Location
- chrX:123621356 (GRCh38)
- Structure
- AlphaFold pLDDT 72.83 · 4 PDB
- Residue 1339
- the 'charged domain' region; the 'disordered' 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-asp1339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown