RASA2 p.Leu769Phe
c.2307A>T · rs141310259 · VCV1426227
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.039%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.105 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.99 | GERP -3.4, phastCons 0.99 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 3,730 bp · p 5.3e-05 · regional, not allelic |
| Overall | ||
| CADD | 13.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.039%
African / African-American · 29/74,416 alleles
Filtering AF
0.0279%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0241%
Overall
0.00295%
47/1,593,656 alleles · ultra-rare
exomes 24/1,441,456 · genomes 23/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.039% | 2,566 |
| Remaining individualsnot grpmax-eligible | 0.00811% | 12,334 |
| Admixed American | 0.00335% | 29,807 |
| European (non-Finnish) | 0.000945% | 105,784 |
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.Leu769Phe
- Coding
- c.2307A>T
- MANE Select
- NM_006506
- dbSNP
- rs141310259
- Type
- single nucleotide variant
- Location
- chr3:141609501 (GRCh38)
- Gene constraint
- LOEUF 1.484 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.63
Similar variants
- 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
- RASA2 p.Ala742Val Uncertain significance ★★ same type
- RASA2 p.Arg117His Uncertain significance ★★ same type
- RASA2 p.Arg310Gln Uncertain significance ★★ same type
- RASA2 p.Arg366Gln 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-leu769phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown