Is KDM1A p.Pro765Ser (c.2293C>T) pathogenic?

KDM1A p.Pro765Ser (c.2293C>T) is classified Uncertain significance in KDM1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-24). AlphaMissense: likely pathogenic (0.9281); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KDM1A p.Pro765Ser (c.2293C>T)?

KDM1A p.Pro765Ser (c.2293C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KDM1A p.Pro765Ser (c.2293C>T) in the general population?

KDM1A p.Pro765Ser (c.2293C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM1A p.Pro765Ser (c.2293C>T)?

AlphaMissense predicts likely pathogenic (score 0.9281) — an in-silico prediction, not a clinical call.

KDM1A p.Pro765Ser

c.2293C>T · VCV4042154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9281	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -10.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 11 kb · p 2.1e-28 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P741S vs ClinVar P765S) — verify the residue.

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: KDM1A
Protein: p.Pro765Ser
Coding: c.2293C>T
MANE Select: NM_001009999
Type: single nucleotide variant
Location: chr1:23081568 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 129 PDB
Residue 741 UniProt numbering: an α-helix; 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.Pro765= Likely benign ★ 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-pro765ser (accessed [today's date]).

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