Is KDM2B p.Ser477= (c.1431G>A) pathogenic?

KDM2B p.Ser477= (c.1431G>A) is classified Likely benign in KDM2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Very rare (popmax 0.00768%, sas); Associated with KDM2B-related disorder.

What condition is associated with KDM2B p.Ser477= (c.1431G>A)?

KDM2B p.Ser477= (c.1431G>A) is associated with KDM2B-related disorder (ClinVar).

How common is KDM2B p.Ser477= (c.1431G>A) in the general population?

KDM2B p.Ser477= (c.1431G>A) is very rare (popmax 0.00768%, sas) (gnomAD).

KDM2B p.Ser477=

c.1431G>A · rs201253347 · VCV3050555

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Conditions

KDM2B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.6
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00366% 59/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,414
South Asiangrpmax	0.00768%	13,013
African / African-American	0.00534%	18,729
European (non-Finnish)	0.00339%	29,501
East Asian	0.00223%	44,878
Admixed American	0.00167%	60,006

Remaining individuals 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: KDM2B
Protein: p.Ser477=
Coding: c.1431G>A
MANE Select: NM_032590
dbSNP: rs201253347
Type: single nucleotide variant
Location: chr12:121509783 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB
Residue 477: a modified residue (phosphoserine)

Full KDM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KDM2B-related disorder

Similar variants

KDM2B p.Ser477Leu Uncertain significance ★ ⚠ same residue
KDM2B p.Arg614Pro Pathogenic/Likely pathogenic ★★ same condition
KDM2B p.Cys616Arg Pathogenic/Likely pathogenic ★★ same condition
KDM2B c.778-2A>G Likely pathogenic ★ same condition
KDM2B p.Cys627Ser Pathogenic ★ same condition
KDM2B p.Glu896Ter Uncertain significance ★ same condition
KDM2B p.Gly789Ser Uncertain significance ★ ⚠ same condition
KDM2B p.His781Arg 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/kdm2b-p-ser477 (accessed [today's date]).

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