Is KDM1A p.Pro153= (c.459A>G) pathogenic?

KDM1A p.Pro153= (c.459A>G) is classified Likely benign in KDM1A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-30). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with KDM1A p.Pro153= (c.459A>G)?

KDM1A p.Pro153= (c.459A>G) is associated with Inborn genetic diseases (ClinVar).

How common is KDM1A p.Pro153= (c.459A>G) in the general population?

KDM1A p.Pro153= (c.459A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

KDM1A p.Pro153=

c.459A>G · VCV3257233

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.9
Overall
CADD	1.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,762 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000745% 12/1,610,782 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,762
European (non-Finnish)	0.000933%	107,162

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: KDM1A
Protein: p.Pro153=
Coding: c.459A>G
MANE Select: NM_001009999
Type: single nucleotide variant
Location: chr1:23030576 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 129 PDB
Residue 153: the 'disordered' region

Full KDM1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM1A p.Ala10Val Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala11Ser Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala11Thr Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala12Val Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala13Thr Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala18Thr Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala197Thr Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala558Gly 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/kdm1a-p-pro153 (accessed [today's date]).

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