WHRN p.Pro646=
c.1938C>A · rs144952955 · VCV1649897
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0254%, afr)
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 2.5 | GERP 0.93, phastCons 1 |
| Overall | ||
| CADD | 6.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0254%
African / African-American · 19/74,944 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00124%
20/1,613,664 alleles · ultra-rare
exomes 9/1,461,418 · genomes 11/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0254% | 3,944 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
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.Pro646=
- Coding
- c.1938C>A
- MANE Select
- NM_015404
- dbSNP
- rs144952955
- Type
- single nucleotide variant
- Location
- chr9:114406653 (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 646
- the 'disordered' region
Similar variants
- WHRN p.Pro646Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown