AHRR p.Pro452=
c.1356G>A · VCV4028631
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0184%, 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 -2.8 | GERP -2.6 |
| Overall | ||
| CADD | 1.818 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0184%
Admixed American · 11/59,908 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00796%
Overall
0.00341%
55/1,612,836 alleles · ultra-rare
exomes 47/1,460,790 · genomes 8/152,046 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0184% | 5,446 |
| Middle Eastern | 0.0164% | 6,080 |
| African / African-American | 0.00801% | 12,477 |
| European (non-Finnish) | 0.00305% | 32,776 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
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
- AHRR
- Protein
- p.Pro452=
- Coding
- c.1356G>A
- MANE Select
- NM_001377236
- Type
- single nucleotide variant
- Location
- chr5:434096 (GRCh38)
- Gene constraint
- LOEUF 0.897 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.28 · 1 PDB
- Residue 452
- the 'disordered' region
Similar variants
- AHRR p.Arg453Cys Benign ★★ same type
- AHRR c.709-131C>G Uncertain significance ★ same type
- AHRR c.709-143C>T Uncertain significance ★ same type
- AHRR c.709-147G>T Uncertain significance ★ same type
- AHRR c.709-166G>A Uncertain significance ★ same type
- AHRR c.709-167C>T Uncertain significance ★ same type
- AHRR p.Ala194Val Uncertain significance ★ ⚠ same type
- AHRR p.Ala24Thr 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/ahrr-p-pro452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown