Is KDM3B p.Pro780= (c.2340G>A) pathogenic?

KDM3B p.Pro780= (c.2340G>A) is classified Benign in KDM3B (ClinVar, Single submitter, 3 submitters; last evaluated 2022-05-01). Ultra-rare (popmax 0.0669%, eas).

How common is KDM3B p.Pro780= (c.2340G>A) in the general population?

KDM3B p.Pro780= (c.2340G>A) is ultra-rare (popmax 0.0669%, eas) (gnomAD).

KDM3B p.Pro780=

c.2340G>A · rs187275789 · VCV2655718

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	acceptor loss, 5 bp away · masked 0 · deltas
Pangolin	Δ0.35	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 1.9	GERP -4.2, phastCons 1
Overall
CADD	13.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0669% East Asian · 30/44,816 alleles

Filtering AF 0.0482% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.0182% 294/1,613,060 alleles · ultra-rare exomes 258/1,460,802 · genomes 36/152,258 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.348%	287
Finnishnot grpmax-eligible	0.0828%	1,208
East Asiangrpmax	0.0669%	1,494
Remaining individualsnot grpmax-eligible	0.0432%	2,313
South Asian	0.0165%	6,072
European (non-Finnish)	0.00534%	18,716
African / African-American	0.00267%	37,513
Admixed American	0.00167%	60,016

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KDM3B
Protein: p.Pro780=
Coding: c.2340G>A
MANE Select: NM_016604
dbSNP: rs187275789
Type: single nucleotide variant
Location: chr5:138391972 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.78 · 36 PDB
Residue 780: a UniProt-annotated variant site (in dijos)

Full KDM3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM3B p.Ala1543Thr Likely pathogenic ★★ same type
KDM3B p.Arg1472Ter Likely pathogenic ★★ same type
KDM3B p.Arg1517Ter Pathogenic/Likely pathogenic ★★ same type
KDM3B p.Arg943Gln Pathogenic/Likely pathogenic ★★ same type
KDM3B p.Tyr1544Cys Pathogenic ★★ same type
KDM3B p.Ala31Val Uncertain significance ★★ ⚠ same type
KDM3B p.Ala865Val Uncertain significance ★★ ⚠ same type
KDM3B p.Arg1659His Uncertain significance ★★ ⚠ same type

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/kdm3b-p-pro780 (accessed [today's date]).

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