KDM2A p.Arg175Ser
c.525G>C · VCV3287877
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9846 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9846 | likely pathogenic |
|---|---|---|
| REVEL | 0.496 | indeterminate |
| SaProt | LLR -9.93 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.17 | constrained · MANE · 20 kb · p 3.9e-40 · regional, not allelic |
| Overall | ||
| CADD | 24.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- KDM2A
- Protein
- p.Arg175Ser
- Coding
- c.525G>C
- MANE Select
- NM_012308
- Type
- single nucleotide variant
- Location
- chr11:67215378 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.87 · 7 PDB
- Residue 175
- the jmjc domain; an α-helix
Similar variants
- KDM2A p.His284Tyr Likely pathogenic ★★ same type
- KDM2A p.Met591Thr Likely pathogenic ★★ same type
- KDM2A p.Cys1151= Benign ★★ same type
- KDM2A p.Thr351= Benign ★★ same type
- KDM2A p.Arg20Ter Pathogenic ★ same type
- KDM2A p.Arg319Gln Likely pathogenic ★ same type
- KDM2A p.Arg383Ter Pathogenic ★ same type
- KDM2A p.Arg568Gln Likely pathogenic ★ 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/kdm2a-p-arg175ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown