RFWD3 p.Pro494=
c.1482G>A · rs769001463 · VCV1972917
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -3.7 | |
| Overall | ||
| CADD | 6.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,018 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000496%
8/1,614,102 alleles · very rare
exomes 8/1,461,858 · genomes 0/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,006 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Pro494=
- Coding
- c.1482G>A
- MANE Select
- NM_018124
- dbSNP
- rs769001463
- Type
- single nucleotide variant
- Location
- chr16:74632618 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.95 · 1 PDB
- Residue 494
- a β-strand
Similar variants
- RFWD3 p.Pro494Leu 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-pro494 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown