Is KAT6A p.Pro1736= (c.5208A>G) pathogenic?

KAT6A p.Pro1736= (c.5208A>G) is classified Benign/Likely benign in KAT6A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-07). Ultra-rare (popmax 0.0143%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KAT6A p.Pro1736= (c.5208A>G)?

KAT6A p.Pro1736= (c.5208A>G) is associated with Inborn genetic diseases (ClinVar).

How common is KAT6A p.Pro1736= (c.5208A>G) in the general population?

KAT6A p.Pro1736= (c.5208A>G) is ultra-rare (popmax 0.0143%, nfe) (gnomAD).

KAT6A p.Pro1736=

c.5208A>G · rs147230777 · VCV1746076

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -5.3, phastCons 0.008
Overall
CADD	3.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% European (non-Finnish) · 169/1,180,028 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0413% 666/1,614,102 alleles · ultra-rare exomes 558/1,461,886 · genomes 108/152,216 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.737%	136
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)grpmax	0.0143%	6,982
African / African-American	0.00133%	74,992

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KAT6A
Protein: p.Pro1736=
Coding: c.5208A>G
MANE Select: NM_006766
dbSNP: rs147230777
Type: single nucleotide variant
Location: chr8:41933012 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 1736: the 'interaction with pml' region

Full KAT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6A p.Pro1736Leu Uncertain significance ★ ⚠ same residue
KAT6A p.Pro1736Ser Uncertain significance ★ ⚠ same residue
KAT6A p.Arg1129Ter Pathogenic ★★ same condition
KAT6A p.Arg148Ter Pathogenic ★★ same condition
KAT6A p.Arg286Ter Pathogenic ★★ same condition
KAT6A p.Arg735Ter Pathogenic ★★ same condition
KAT6A p.Ala1451Gly Uncertain significance ★★ ⚠ same condition
KAT6A p.Ala492Val 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/kat6a-p-pro1736 (accessed [today's date]).

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