Is KDM2B p.Phe1288Ser (c.3863T>C) pathogenic?

KDM2B p.Phe1288Ser (c.3863T>C) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely pathogenic (0.9005); Very rare (popmax 0.00167%, amr).

How common is KDM2B p.Phe1288Ser (c.3863T>C) in the general population?

KDM2B p.Phe1288Ser (c.3863T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KDM2B p.Phe1288Ser (c.3863T>C)?

AlphaMissense predicts likely pathogenic (score 0.9005) — an in-silico prediction, not a clinical call.

KDM2B p.Phe1288Ser

c.3863T>C · rs782287592 · VCV2885855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9005 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9005	likely pathogenic
REVEL	0.179	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP -0.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 12 kb · p 1.8e-13 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,984 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,946 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,984
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000169%	589,998

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.Phe1288Ser
Coding: c.3863T>C
MANE Select: NM_032590
dbSNP: rs782287592
Type: single nucleotide variant
Location: chr12:121430436 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB
Residue 1288: an α-helix; a UniProt-annotated variant site (in nedcro; uncertain significance)

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

Similar variants

KDM2B p.Arg614Pro Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Cys616Arg Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Gly638Asp Pathogenic ★★ same type
KDM2B p.Arg1124Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg294Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg612Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Asn742Lys Uncertain significance ★★ ⚠ same type
KDM2B p.Glu922Lys 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/kdm2b-p-phe1288ser (accessed [today's date]).

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