Is KDM1A p.Pro65= (c.195T>A) pathogenic?

KDM1A p.Pro65= (c.195T>A) is classified Likely benign in KDM1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). Very rare (popmax 0.000188%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KDM1A p.Pro65= (c.195T>A)?

KDM1A p.Pro65= (c.195T>A) is associated with Inborn genetic diseases (ClinVar).

How common is KDM1A p.Pro65= (c.195T>A) in the general population?

KDM1A p.Pro65= (c.195T>A) is very rare (popmax 0.000188%, nfe) (gnomAD).

KDM1A p.Pro65=

c.195T>A · rs2522471831 · VCV2879513

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000188%, nfe)

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 -0.004	GERP -1.1, phastCons 0.82
Overall
CADD	13.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000188% European (non-Finnish) · 2/1,066,452 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000145% 2/1,381,316 alleles · very rare exomes 2/1,229,388 · genomes 0/151,928 · 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: KDM1A
Protein: p.Pro65=
Coding: c.195T>A
MANE Select: NM_001009999
dbSNP: rs2522471831
Type: single nucleotide variant
Location: chr1:23019791 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 129 PDB
Residue 65: 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.Pro65Arg Uncertain significance ★★ ⚠ same residue
KDM1A p.Pro65Leu Uncertain significance ★ ⚠ same residue
KDM1A p.Pro65Ser Uncertain significance ★ ⚠ same residue
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

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-pro65 (accessed [today's date]).

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