TOP6BL p.Ser329=
c.987A>G · rs182460002 · VCV2642008
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0619%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.61 | GERP -5.5 |
| Overall | ||
| CADD | 4.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0619%
South Asian · 52/84,030 alleles
Filtering AF
0.0484%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0436%
Overall
0.0248%
385/1,552,080 alleles · ultra-rare
exomes 351/1,400,070 · genomes 34/152,010 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0619% | 1,616 |
| Middle Eastern | 0.0333% | 2,999 |
| Remaining individualsnot grpmax-eligible | 0.0282% | 3,548 |
| European (non-Finnish) | 0.0255% | 3,928 |
| Finnishnot grpmax-eligible | 0.0233% | 4,299 |
| Admixed American | 0.0098% | 10,204 |
| African / African-American | 0.00411% | 24,359 |
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
- TOP6BL
- Protein
- p.Ser329=
- Coding
- c.987A>G
- MANE Select
- NM_001302084
- dbSNP
- rs182460002
- Type
- single nucleotide variant
- Location
- chr11:66822587 (GRCh38)
- Structure
- AlphaFold pLDDT 68.14
- Residue 329
- a UniProt-annotated variant site (found in a patient with spermatogenic failure characterized by defects in programmed meiotic dna double-strand break formation; pathogenic)
Similar variants
- TOP6BL c.-30+3538A>G Uncertain significance ★ ⚠ same type
- TOP6BL p.Ala406Thr Uncertain significance ★ ⚠ same type
- TOP6BL p.Arg374Cys Uncertain significance ★ ⚠ same type
- TOP6BL p.Asp232His Uncertain significance ★ ⚠ same type
- TOP6BL p.His131Asn Uncertain significance ★ same type
- TOP6BL p.Met352Arg Uncertain significance ★ ⚠ same type
- TOP6BL p.Pro200Leu Uncertain significance ★ ⚠ same type
- TOP6BL p.Ser336Pro 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/top6bl-p-ser329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown