Is KAT6B p.Pro404Ser (c.1210C>T) pathogenic?

KAT6B p.Pro404Ser (c.1210C>T) is classified Uncertain significance in KAT6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-24). AlphaMissense: likely pathogenic (0.6171); Absent from gnomAD v4.1; Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Pro404Ser (c.1210C>T)?

KAT6B p.Pro404Ser (c.1210C>T) is associated with genitopatellar syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Pro404Ser (c.1210C>T) in the general population?

KAT6B p.Pro404Ser (c.1210C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6B p.Pro404Ser (c.1210C>T)?

AlphaMissense predicts likely pathogenic (score 0.6171) — an in-silico prediction, not a clinical call.

KAT6B p.Pro404Ser

c.1210C>T · rs2548951794 · VCV2850281

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6171 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.6171	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -4.75	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 9,183 bp · p 4.6e-05 · regional, not allelic
Overall
CADD	24.6	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

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.Pro404Ser
Coding: c.1210C>T
MANE Select: NM_012330
dbSNP: rs2548951794
Type: single nucleotide variant
Location: chr10:74975547 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 404: the 'disordered' region; the 'negatively regulates hat activity' 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 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-pro404ser (accessed [today's date]).

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