KSR2 p.Asp577=
c.1731T>C · VCV3354429
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
Conditions
1
KSR2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.48 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 13.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,630 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,613,498 alleles · very rare
exomes 6/1,461,194 · genomes 0/152,304 · joint denominator
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
- KSR2
- Protein
- p.Asp577=
- Coding
- c.1731T>C
- MANE Select
- NM_173598
- Type
- single nucleotide variant
- Location
- chr12:117531012 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.22 · 9 PDB
Disease context
KSR2-related disorder
Similar variants
- KSR2 p.Arg745Gln Uncertain significance ★★ ⚠ same condition
- KSR2 p.Gln665His Uncertain significance ★★ ⚠ same condition
- KSR2 p.Leu546Pro Uncertain significance ★★ ⚠ same condition
- KSR2 p.Pro171Ser Uncertain significance ★★ ⚠ same condition
- KSR2 c.1802+2T>A Likely pathogenic ★ same condition
- KSR2 p.Arg192Leu Uncertain significance ★ ⚠ same condition
- KSR2 p.Arg296Leu Uncertain significance ★ ⚠ same condition
- KSR2 p.Arg643Gln Uncertain significance ★ ⚠ same condition
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/ksr2-p-asp577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown