RFWD3 p.Ser63=
c.189C>T · rs989059672 · VCV1990855
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0306%, afr)
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 1.1 | GERP -0.71, phastCons 0.59 |
| Overall | ||
| CADD | 3.578 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0306%
African / African-American · 23/75,046 alleles
Filtering AF
0.0209%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0177%
Overall
0.00167%
27/1,614,142 alleles · ultra-rare
exomes 22/1,461,876 · genomes 5/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0306% | 3,263 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| South Asian | 0.0011% | 91,084 |
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.Ser63=
- Coding
- c.189C>T
- MANE Select
- NM_018124
- dbSNP
- rs989059672
- Type
- single nucleotide variant
- Location
- chr16:74661261 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.95 · 1 PDB
- Residue 63
- a modified residue (phosphoserine; by atm and atr)
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-ser63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown