Is KAT6B p.Thr2016= (c.6048G>A) pathogenic?

KAT6B p.Thr2016= (c.6048G>A) is classified Benign/Likely benign in KAT6B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-05). Rare (popmax 0.753%, eas); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Thr2016= (c.6048G>A)?

KAT6B p.Thr2016= (c.6048G>A) is associated with genitopatellar syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Thr2016= (c.6048G>A) in the general population?

KAT6B p.Thr2016= (c.6048G>A) is rare (popmax 0.753%, eas) (gnomAD).

KAT6B p.Thr2016=

c.6048G>A · rs116978399 · VCV1278561

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.753%, eas)

Conditions

genitopatellar syndrome

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 -8.2	GERP -3.9
Overall
CADD	0.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.753% East Asian · 338/44,874 alleles

Filtering AF 0.687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.661%

Overall 0.0222% 359/1,614,026 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.753%	133
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.00333%	30,006
Finnishnot grpmax-eligible	0.00313%	31,996
European (non-Finnish)	0.000424%	236,000

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: KAT6B
Protein: p.Thr2016=
Coding: c.6048G>A
MANE Select: NM_012330
dbSNP: rs116978399
Type: single nucleotide variant
Location: chr10:75030872 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 2016: the 'interaction with runx1 and runx2' region

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

Disease context

genitopatellar syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: blepharophimosis - intellectual disability syndrome, SBBYS type

Similar variants

KAT6B p.Thr2016Met Uncertain significance ★ ⚠ same residue
KAT6B c.3664+1G>A Pathogenic ★★ same condition
KAT6B p.Arg1058Ter Pathogenic ★★ same condition
KAT6B p.Arg1797Ter Pathogenic ★★ same condition
KAT6B p.Arg783Ter Pathogenic/Likely pathogenic ★★ same condition
KAT6B p.Gln1014Ter Pathogenic ★★ same condition
KAT6B p.Gln1752Ter Pathogenic ★★ same condition
KAT6B p.Gln1768Ter 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-thr2016 (accessed [today's date]).

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