RASA2 p.Ser849Phe
c.2546C>T · rs140787611 · VCV2504029
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0498%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.182 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Pangolin | Δ0.22 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 0.84, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 3,730 bp · p 5.3e-05 · regional, not allelic |
| Overall | ||
| CADD | 22.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0498%
Middle Eastern · 3/6,024 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00722%
Overall
0.000441%
7/1,588,644 alleles · ultra-rare
exomes 6/1,436,514 · genomes 1/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0498% | 2,008 |
| Admixed American | 0.00173% | 57,774 |
| European (non-Finnish) | 0.000258% | 387,522 |
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.Ser849Phe
- Coding
- c.2546C>T
- MANE Select
- NM_006506
- dbSNP
- rs140787611
- Type
- single nucleotide variant
- Location
- chr3:141612309 (GRCh38)
- Gene constraint
- LOEUF 1.484 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.63
- Residue 849
- the 'disordered' region
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-ser849phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown