WHRN p.Pro706=
c.2118A>G · rs756217407 · VCV1097132
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.13 | GERP -4, phastCons 0.8 |
| Overall | ||
| CADD | 1.453 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
South Asian · 35/91,076 alleles
Filtering AF
0.0283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00248%
40/1,613,776 alleles · ultra-rare
exomes 39/1,461,744 · genomes 1/152,032 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0384% | 2,602 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,825 |
| African / African-American | 0.00134% | 74,872 |
| European (non-Finnish) | 8.47e-05% | 1,180,006 |
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
- WHRN
- Protein
- p.Pro706=
- Coding
- c.2118A>G
- MANE Select
- NM_015404
- dbSNP
- rs756217407
- Type
- single nucleotide variant
- Location
- chr9:114406473 (GRCh38)
- Gene constraint
- LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 59.39 · 5 PDB
- Residue 706
- the 'disordered' region
Similar variants
- WHRN c.1203+2T>C Likely pathogenic ★★ same type
- WHRN c.1417-1G>A Pathogenic/Likely pathogenic ★★ same type
- WHRN p.Arg778Ter Pathogenic ★★ same type
- WHRN p.Gln187Ter Pathogenic/Likely pathogenic ★★ same type
- WHRN p.Trp374Ter Pathogenic/Likely pathogenic ★★ same type
- WHRN c.*156G>A Uncertain significance ★★ same type
- WHRN p.Ala207Ser Uncertain significance ★★ ⚠ same type
- WHRN p.Ala315Pro 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/whrn-p-pro706 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown