PRDM9 p.Thr681=
c.2043T>A · rs200743042 · VCV2655373
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0676%, amr)
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 -8.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.972 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0676%
Admixed American · 11/16,278 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.0241%
92/381,628 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0676% | 1,480 |
| Remaining individualsnot grpmax-eligible | 0.0564% | 1,772 |
| Middle Eastern | 0.0342% | 2,920 |
| African / African-American | 0.0285% | 3,505 |
| Finnishnot grpmax-eligible | 0.0232% | 4,319 |
| European (non-Finnish) | 0.0225% | 4,454 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0218% | 4,591 |
| East Asian | 0.0135% | 7,401 |
| South Asian | 0.00278% | 35,936 |
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
- PRDM9
- Protein
- p.Thr681=
- Coding
- c.2043T>A
- MANE Select
- NM_020227
- dbSNP
- rs200743042
- Type
- single nucleotide variant
- Location
- chr5:23527131 (GRCh38)
- Gene constraint
- LOEUF 1.039 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.19 · 5 PDB
- Residue 681
- a UniProt-annotated variant site (in allele a)
Similar variants
- PRDM9 p.Thr681Ser Benign/Likely benign ★★ ⚠ same residue
- PRDM9 p.Thr681Ala Uncertain significance ★ ⚠ same residue
- PRDM9 c.301+67A>G Benign ★★ same type
- PRDM9 c.509-41C>T Benign ★★ same type
- PRDM9 c.883-52C>T Benign ★★ same type
- PRDM9 c.*125G>A Benign ★★ same type
- PRDM9 c.*37A>G Benign ★★ same type
- PRDM9 p.Asn790His Likely benign ★★ 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/prdm9-p-thr681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown