Is KDM2B p.Pro787Leu (c.2360C>T) pathogenic?

KDM2B p.Pro787Leu (c.2360C>T) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-11). AlphaMissense: likely benign (0.0712); Ultra-rare (popmax 0.0826%, afr); Associated with Inborn genetic diseases.

What condition is associated with KDM2B p.Pro787Leu (c.2360C>T)?

KDM2B p.Pro787Leu (c.2360C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KDM2B p.Pro787Leu (c.2360C>T) in the general population?

KDM2B p.Pro787Leu (c.2360C>T) is ultra-rare (popmax 0.0826%, afr) (gnomAD).

What do computational predictors say about KDM2B p.Pro787Leu (c.2360C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

KDM2B p.Pro787Leu

c.2360C>T · rs369468363 · VCV2457916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.024, phastCons 0.97
Regional constraint	o/e 1.04	unconstrained · MANE · 1,864 bp · p 0.44 · regional, not allelic
Overall
CADD	17.25	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% African / African-American · 62/75,064 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.00533% 86/1,613,694 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0826%	1,211
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00333%	30,013
South Asian	0.0011%	91,088
European (non-Finnish)	0.000763%	131,116

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: KDM2B
Protein: p.Pro787Leu
Coding: c.2360C>T
MANE Select: NM_032590
dbSNP: rs369468363
Type: single nucleotide variant
Location: chr12:121444103 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB
Residue 787: the 'disordered' region

Full KDM2B 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

KDM2B p.Pro787Ser Uncertain significance ★ ⚠ same residue
KDM2B p.Arg294Gln Uncertain significance ★★ ⚠ same condition
KDM2B p.Arg612Gln Uncertain significance ★★ ⚠ same condition
KDM2B p.Asn742Lys Uncertain significance ★★ ⚠ same condition
KDM2B p.Glu922Lys Uncertain significance ★★ ⚠ same condition
KDM2B p.Val157Met Uncertain significance ★★ ⚠ same condition
KDM2B p.Glu894Lys Likely benign ★★ ⚠ same condition
KDM2B p.Cys616Phe Pathogenic ★ 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/kdm2b-p-pro787leu (accessed [today's date]).

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