Is KAT6B p.Pro1785= (c.5355C>T) pathogenic?

KAT6B p.Pro1785= (c.5355C>T) is classified Benign/Likely benign in KAT6B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-21). Ultra-rare (popmax 0.0706%, afr); Associated with blepharophimosis - intellectual disability syndrome, SBBYS type.

How common is KAT6B p.Pro1785= (c.5355C>T) in the general population?

KAT6B p.Pro1785= (c.5355C>T) is ultra-rare (popmax 0.0706%, afr) (gnomAD).

KAT6B p.Pro1785=

Q: What condition is associated with KAT6B p.Pro1785= (c.5355C>T)?

KAT6B p.Pro1785= (c.5355C>T) is associated with blepharophimosis - intellectual disability syndrome, SBBYS type, genitopatellar syndrome (ClinVar).

c.5355C>T · rs138711901 · VCV260247

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0706%, afr)

Conditions

blepharophimosis - intellectual disability syndrome, SBBYS type

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 -13	GERP -3.6
Overall
CADD	0.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0706% African / African-American · 53/75,068 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00434% 70/1,614,238 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0706%	1,416
Remaining individualsnot grpmax-eligible	0.0048%	20,837
East Asian	0.00446%	22,444
Admixed American	0.00167%	60,028
South Asian	0.0011%	91,090
European (non-Finnish)	0.000847%	118,005

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.Pro1785=
Coding: c.5355C>T
MANE Select: NM_012330
dbSNP: rs138711901
Type: single nucleotide variant
Location: chr10:75030179 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1785: the 'interaction with runx1 and runx2' region

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

Disease context

blepharophimosis - intellectual disability syndrome, SBBYS type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: genitopatellar syndrome

Similar variants

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
KAT6B p.Glu1073Ter 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-pro1785 (accessed [today's date]).

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