Is KDM1A p.Pro765= (c.2295T>A) pathogenic?

KDM1A p.Pro765= (c.2295T>A) is classified Likely benign in KDM1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KDM1A p.Pro765= (c.2295T>A)?

KDM1A p.Pro765= (c.2295T>A) is associated with Inborn genetic diseases (ClinVar).

How common is KDM1A p.Pro765= (c.2295T>A) in the general population?

KDM1A p.Pro765= (c.2295T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

KDM1A p.Pro765=

c.2295T>A · VCV4091058

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.11	GERP 0.28, phastCons 0.86
Overall
CADD	8.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,982 alleles

Overall 6.2e-05% 1/1,613,946 alleles · very rare exomes 0/1,461,776 · genomes 1/152,170 · 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.Pro765=
Coding: c.2295T>A
MANE Select: NM_001009999
Type: single nucleotide variant
Location: chr1:23081570 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 129 PDB
Residue 765: a β-strand; the 'demethylase activity' region; a UniProt-annotated variant site (in aimah3; likely pathogenic; loss of protein expression in patient adrenal samples); a UniProt-annotated variant site (in aimah3; likely pathogenic)

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.Pro765Ser 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
KDM1A p.Ala18Thr Uncertain significance ★★ ⚠ same condition
KDM1A p.Ala197Thr 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-pro765 (accessed [today's date]).

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