Is KAT6B p.Pro2000Ser (c.5998C>T) pathogenic?

KAT6B p.Pro2000Ser (c.5998C>T) is classified Uncertain significance in KAT6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.3636); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KAT6B p.Pro2000Ser (c.5998C>T)?

KAT6B p.Pro2000Ser (c.5998C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KAT6B p.Pro2000Ser (c.5998C>T) in the general population?

KAT6B p.Pro2000Ser (c.5998C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6B p.Pro2000Ser (c.5998C>T)?

AlphaMissense predicts ambiguous (score 0.3636) — an in-silico prediction, not a clinical call.

KAT6B p.Pro2000Ser

c.5998C>T · VCV3531870

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3636 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3636	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -6.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 979 bp · p 0.00018 · regional, not allelic
Overall
CADD	22.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KAT6B
Protein: p.Pro2000Ser
Coding: c.5998C>T
MANE Select: NM_012330
Type: single nucleotide variant
Location: chr10:75030822 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 2000: the 'interaction with runx1 and runx2' region

Full KAT6B 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

KAT6B p.Gln1768Ter Pathogenic ★★ same condition
KAT6B p.Ala1317Thr Uncertain significance ★★ ⚠ same condition
KAT6B p.Arg151Gln Uncertain significance ★★ ⚠ same condition
KAT6B p.Arg1898Trp Uncertain significance ★★ ⚠ same condition
KAT6B p.Arg406Trp Uncertain significance ★★ ⚠ same condition
KAT6B p.Arg899Cys Uncertain significance ★★ ⚠ same condition
KAT6B p.Asn680Tyr Uncertain significance ★★ ⚠ same condition
KAT6B p.Cys1244Gly 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/kat6b-p-pro2000ser (accessed [today's date]).

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