Is KAT6A p.Ser28= (c.84A>G) pathogenic?

KAT6A p.Ser28= (c.84A>G) is classified Benign in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). Very rare (popmax 8.47e-05%, nfe).

How common is KAT6A p.Ser28= (c.84A>G) in the general population?

KAT6A p.Ser28= (c.84A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

KAT6A p.Ser28=

c.84A>G · rs774292174 · VCV2979751

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -0.5	GERP -4.1, phastCons 0.14
Overall
CADD	8.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 0.000496% 8/1,614,056 alleles · very rare exomes 7/1,461,842 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)grpmax	8.47e-05%	1,180,016

Ashkenazi Jewish 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.Ser28=
Coding: c.84A>G
MANE Select: NM_006766
dbSNP: rs774292174
Type: single nucleotide variant
Location: chr8:42048894 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 28: the samd1-like winged helix (wh) domain; the 'required for activation of runx1-1' region

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

Similar variants

KAT6A c.3353-1G>A Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1012Ter Pathogenic ★★ same type
KAT6A p.Arg1019Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1024Ter Pathogenic ★★ same type
KAT6A p.Arg1129Ter Pathogenic ★★ same type
KAT6A p.Arg148Ter Pathogenic ★★ same type
KAT6A p.Arg220Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg251Ter Likely pathogenic ★★ same type

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-ser28 (accessed [today's date]).

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