Is KAT6B p.Pro1049= (c.3147G>A) pathogenic?

KAT6B p.Pro1049= (c.3147G>A) is classified Pathogenic in KAT6B (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-04-29). Absent from gnomAD v4.1; Associated with KAT6B-related disorder.

What condition is associated with KAT6B p.Pro1049= (c.3147G>A)?

KAT6B p.Pro1049= (c.3147G>A) is associated with KAT6B-related disorder, intellectual disability, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Pro1049= (c.3147G>A) in the general population?

KAT6B p.Pro1049= (c.3147G>A) is absent from gnomAD v4.1 (gnomAD).

KAT6B p.Pro1049=

c.3147G>A · rs886041207 · VCV279815

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

KAT6B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.97	acceptor gain · deltas
Pangolin	Δ0.68	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.9	GERP 0.93, phastCons 1
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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.Pro1049=
Coding: c.3147G>A
MANE Select: NM_012330
dbSNP: rs886041207
Type: single nucleotide variant
Location: chr10:75022006 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1049: the 'disordered' region

Full KAT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KAT6B-related disorder

Also linked: intellectual disability blepharophimosis - intellectual disability syndrome, SBBYS type

Similar variants

KAT6B p.Pro1049Leu Benign ★ same residue
KAT6B c.3664+1G>A Pathogenic ★★ same condition
KAT6B p.Arg1058Ter Pathogenic ★★ same condition
KAT6B p.Arg1797Ter Pathogenic ★★ same condition
KAT6B p.Arg352Ter Pathogenic ★★ same condition
KAT6B p.Arg783Ter Pathogenic/Likely pathogenic ★★ same condition
KAT6B p.Gln1014Ter Pathogenic ★★ same condition
KAT6B p.Gln1117Ter 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/kat6b-p-pro1049 (accessed [today's date]).

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