RFWD3 p.Val652=
c.1956G>C · rs137961728 · VCV740461
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.648%, 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 -0.061 | phastCons 0.63 |
| Overall | ||
| CADD | 5.593 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.648%
African / African-American · 486/75,036 alleles
Filtering AF
0.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.581%
Overall
0.0319%
515/1,614,114 alleles · rare
exomes 247/1,461,798 · genomes 268/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.648% | 154 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| Admixed American | 0.0167% | 6,002 |
| European (non-Finnish) | 0.000508% | 196,669 |
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.Val652=
- Coding
- c.1956G>C
- MANE Select
- NM_018124
- dbSNP
- rs137961728
- Type
- single nucleotide variant
- Location
- chr16:74628465 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.95 · 1 PDB
- Residue 652
- a β-strand
Similar variants
- RFWD3 p.Val652Ala Uncertain significance ★ ⚠ same residue
- 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
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-val652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown