Is KAT6B p.Pro2020Ser (c.6058C>T) pathogenic?

KAT6B p.Pro2020Ser (c.6058C>T) is classified Conflicting classifications of pathogenicity in KAT6B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1824); Ultra-rare (popmax 0.0134%, eas); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Pro2020Ser (c.6058C>T)?

KAT6B p.Pro2020Ser (c.6058C>T) is associated with genitopatellar syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Pro2020Ser (c.6058C>T) in the general population?

KAT6B p.Pro2020Ser (c.6058C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about KAT6B p.Pro2020Ser (c.6058C>T)?

AlphaMissense predicts likely benign (score 0.1824) — an in-silico prediction, not a clinical call.

KAT6B p.Pro2020Ser

c.6058C>T · rs770958025 · VCV3112774

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1824 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.1824	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 979 bp · p 0.00018 · regional, not allelic
Overall
CADD	23.9	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 0.0134% East Asian · 6/44,896 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,614,058 alleles · ultra-rare exomes 4/1,461,870 · genomes 2/152,188 · 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.Pro2020Ser
Coding: c.6058C>T
MANE Select: NM_012330
dbSNP: rs770958025
Type: single nucleotide variant
Location: chr10:75030882 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 2020: the 'interaction with runx1 and runx2' 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 p.Pro2020Ala Uncertain significance ★★ ⚠ same residue
KAT6B p.Pro2020Arg 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

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-pro2020ser (accessed [today's date]).

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