Is KAT6B p.Pro372Ser (c.1114C>T) pathogenic?

KAT6B p.Pro372Ser (c.1114C>T) is classified Uncertain significance in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: likely pathogenic (0.8654); Very rare (popmax 0.00167%, amr); Associated with blepharophimosis - intellectual disability syndrome, SBBYS type.

How common is KAT6B p.Pro372Ser (c.1114C>T) in the general population?

KAT6B p.Pro372Ser (c.1114C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KAT6B p.Pro372Ser (c.1114C>T)?

AlphaMissense predicts likely pathogenic (score 0.8654) — an in-silico prediction, not a clinical call.

KAT6B p.Pro372Ser

Q: What condition is associated with KAT6B p.Pro372Ser (c.1114C>T)?

KAT6B p.Pro372Ser (c.1114C>T) is associated with blepharophimosis - intellectual disability syndrome, SBBYS type, genitopatellar syndrome (ClinVar).

c.1114C>T · VCV3597411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

blepharophimosis - intellectual disability syndrome, SBBYS type

Computational evidence

Protein change
AlphaMissense	0.8654	likely pathogenic
REVEL	0.44	indeterminate
SaProt	LLR -4.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 9,183 bp · p 4.6e-05 · regional, not allelic
Overall
CADD	27.2	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 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000124% 2/1,614,108 alleles · very rare exomes 2/1,461,870 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	8.47e-05%	1,180,022

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.Pro372Ser
Coding: c.1114C>T
MANE Select: NM_012330
Type: single nucleotide variant
Location: chr10:74975451 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 372: 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

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

Also linked: genitopatellar syndrome

Similar variants

KAT6B p.Pro372Leu 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-pro372ser (accessed [today's date]).

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