Is KDM3A p.Pro780= (c.2340G>A) pathogenic?

KDM3A p.Pro780= (c.2340G>A) is classified Benign in KDM3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-11). Common (popmax 6.59%, eas) — too common for a highly-penetrant pathogenic allele; Associated with KDM3A-related disorder.

What condition is associated with KDM3A p.Pro780= (c.2340G>A)?

KDM3A p.Pro780= (c.2340G>A) is associated with KDM3A-related disorder (ClinVar).

KDM3A p.Pro780=

Q: How common is KDM3A p.Pro780= (c.2340G>A) in the general population?

KDM3A p.Pro780= (c.2340G>A) is common (popmax 6.59%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2340G>A · rs61748134 · VCV3059965

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.59%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

KDM3A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.5	GERP -5.4
Overall
CADD	8.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.59% East Asian · 2,958/44,884 alleles

Filtering AF 6.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.31%

Overall 2.12% 34,184/1,612,826 alleles · common exomes 31,444/1,460,544 · genomes 2,740/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	6.59%	15
Amishnot grpmax-eligible	4.71%	21
Middle Eastern	3.24%	31
Remaining individualsnot grpmax-eligible	2.54%	39
European (non-Finnish)	2.18%	46
South Asian	1.92%	52
Admixed American	1.54%	65
Ashkenazi Jewishnot grpmax-eligible	0.763%	131
Finnishnot grpmax-eligible	0.733%	137
African / African-American	0.424%	236

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: KDM3A
Protein: p.Pro780=
Coding: c.2340G>A
MANE Select: NM_018433
dbSNP: rs61748134
Type: single nucleotide variant
Location: chr2:86480190 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.06

Full KDM3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KDM3A-related disorder

Similar variants

KDM3A p.Pro780Leu Uncertain significance ★ ⚠ same residue
KDM3A p.His1204Tyr Uncertain significance ⚠ same condition
KDM3A c.754+9T>C Likely benign same condition
KDM3A p.Ala1261= Benign same condition
KDM3A p.Ala307= Likely benign same condition
KDM3A p.Ala639= Benign same condition
KDM3A p.Ala825= Benign same condition
KDM3A p.Asp152= Likely benign 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/kdm3a-p-pro780 (accessed [today's date]).

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