Is KAT6B p.Ser193Pro (c.577T>C) pathogenic?

KAT6B p.Ser193Pro (c.577T>C) is classified Uncertain significance in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0915); Very rare (popmax 0.000678%, nfe); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Ser193Pro (c.577T>C)?

KAT6B p.Ser193Pro (c.577T>C) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Ser193Pro (c.577T>C) in the general population?

KAT6B p.Ser193Pro (c.577T>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about KAT6B p.Ser193Pro (c.577T>C)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

KAT6B p.Ser193Pro

c.577T>C · rs1028333030 · VCV2064914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 117 kb · p 0.00012 · regional, not allelic
Overall
CADD	18.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,018 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,966 alleles · very rare exomes 8/1,461,688 · genomes 0/152,278 · joint denominator

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.Ser193Pro
Coding: c.577T>C
MANE Select: NM_012330
dbSNP: rs1028333030
Type: single nucleotide variant
Location: chr10:74843434 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB

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.Ser193= 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-ser193pro (accessed [today's date]).

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