RFWD3 p.Pro541=
c.1623T>A · rs7188880 · VCV1271660
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 77.1%, afr) — too common for a highly-penetrant pathogenic allele
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 1.1 | phastCons 0.99 |
| Overall | ||
| CADD | 11.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
77.1%
African / African-American · 57,757/74,944 alleles
Filtering AF
76.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 76.3%
Overall
52.8%
851,355/1,613,364 alleles · common
exomes 761,867/1,461,254 · genomes 89,488/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 77.1% | 1 |
| East Asian | 75.7% | 1 |
| South Asian | 59.9% | 2 |
| Middle Eastern | 57.9% | 2 |
| Amishnot grpmax-eligible | 56.5% | 2 |
| Remaining individualsnot grpmax-eligible | 54.6% | 2 |
| European (non-Finnish) | 50.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 47.8% | 2 |
| Admixed American | 45.6% | 2 |
| Finnishnot grpmax-eligible | 44.7% | 2 |
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
- RFWD3
- Protein
- p.Pro541=
- Coding
- c.1623T>A
- MANE Select
- NM_018124
- dbSNP
- rs7188880
- Type
- single nucleotide variant
- Location
- chr16:74630912 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.95 · 1 PDB
Similar variants
- RFWD3 p.Ala22Pro Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala231Pro Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala244Val Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala24Val Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala372Thr Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala447Gly Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala581Gly Uncertain significance ★★ ⚠ same type
- RFWD3 p.Ala5Thr 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/rfwd3-p-pro541 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown