Is KAT6B p.Pro1111Ser (c.3331C>T) pathogenic?

KAT6B p.Pro1111Ser (c.3331C>T) is classified Uncertain significance in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-11). AlphaMissense: likely pathogenic (0.8723); Very rare (popmax 0.00223%, eas); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Pro1111Ser (c.3331C>T)?

KAT6B p.Pro1111Ser (c.3331C>T) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Pro1111Ser (c.3331C>T) in the general population?

KAT6B p.Pro1111Ser (c.3331C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about KAT6B p.Pro1111Ser (c.3331C>T)?

AlphaMissense predicts likely pathogenic (score 0.8723) — an in-silico prediction, not a clinical call.

KAT6B p.Pro1111Ser

c.3331C>T · rs765279291 · VCV2963932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.8723	likely pathogenic
REVEL	0.2	benign-leaning
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,071 bp · p 8e-06 · regional, not allelic
Overall
CADD	23.4	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 0.00223% East Asian · 1/44,866 alleles

Overall 0.000124% 2/1,613,214 alleles · very rare exomes 2/1,461,076 · genomes 0/152,138 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
Admixed American	0.00167%	60,010

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.Pro1111Ser
Coding: c.3331C>T
MANE Select: NM_012330
dbSNP: rs765279291
Type: single nucleotide variant
Location: chr10:75022190 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1111: the 'disordered' 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

Similar variants

KAT6B p.Pro1111Gln Likely 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.Gln1752Ter Pathogenic ★★ same condition
KAT6B c.2373+6C>A Uncertain significance ★★ same condition
KAT6B c.2374-3T>C Uncertain significance ★★ same condition
KAT6B p.Ala1317Thr 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-pro1111ser (accessed [today's date]).

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