RASA2 p.Arg75Cys
c.223C>T · rs773584568 · VCV1788248
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00226%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.751 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 1.07 | unconstrained · MANE · 121 kb · p 0.039 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00226%
East Asian · 1/44,272 alleles
Filtering AF
0.000768%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000609%
Overall
0.00126%
20/1,591,554 alleles · very rare
exomes 19/1,439,550 · genomes 1/152,004 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00226% | 44,272 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,610 |
| Finnishnot grpmax-eligible | 0.00157% | 63,820 |
| African / African-American | 0.00137% | 73,106 |
| European (non-Finnish) | 0.00128% | 78,228 |
| South Asian | 0.00116% | 85,952 |
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
- RASA2
- Protein
- p.Arg75Cys
- Coding
- c.223C>T
- MANE Select
- NM_006506
- dbSNP
- rs773584568
- Type
- single nucleotide variant
- Location
- chr3:141512252 (GRCh38)
- Gene constraint
- LOEUF 1.484 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.63
- Residue 75
- the c2 1 domain
Similar variants
- RASA2 p.Arg75His Uncertain significance ★★ same residue
- RASA2 p.Arg75= Likely benign ★★ same residue
- RASA2 p.Arg75Gly Uncertain significance ★ same residue
- RASA2 p.Arg75Ser Uncertain significance ★ same residue
- RASA2 c.612-3C>T Uncertain significance ★★ same type
- RASA2 p.Ala360Gly Uncertain significance ★★ same type
- RASA2 p.Ala489Thr Uncertain significance ★★ same type
- RASA2 p.Ala503Ser 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/rasa2-p-arg75cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown