Is KDM2A p.Arg519Ser (c.1557G>T) pathogenic?

KDM2A p.Arg519Ser (c.1557G>T) is classified Uncertain significance in KDM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). AlphaMissense: likely pathogenic (0.9771); Absent from gnomAD v4.1.

How common is KDM2A p.Arg519Ser (c.1557G>T) in the general population?

KDM2A p.Arg519Ser (c.1557G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM2A p.Arg519Ser (c.1557G>T)?

AlphaMissense predicts likely pathogenic (score 0.9771) — an in-silico prediction, not a clinical call.

KDM2A p.Arg519Ser

c.1557G>T · VCV4526976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9771	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 5.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 13 kb · p 2.6e-10 · regional, not allelic
Overall
CADD	24.5	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.Arg519Ser
Coding: c.1557G>T
MANE Select: NM_012308
Type: single nucleotide variant
Location: chr11:67243086 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.87 · 7 PDB

Full KDM2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-arg519ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown