Is KAT2B p.Glu103= (c.309G>A) pathogenic?

KAT2B p.Glu103= (c.309G>A) is classified Benign in KAT2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-09-01). Common (popmax 49.4%, afr) — too common for a highly-penetrant pathogenic allele.

KAT2B p.Glu103=

Q: How common is KAT2B p.Glu103= (c.309G>A) in the general population?

KAT2B p.Glu103= (c.309G>A) is common (popmax 49.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.309G>A · rs3021408 · VCV1258558

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 49.4%, afr) — too common for a highly-penetrant pathogenic allele

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 2.5	GERP 0.41, phastCons 1
Overall
CADD	7.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.4% African / African-American · 36,992/74,842 alleles

Filtering AF 49% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.8%

Overall 39.5% 636,826/1,610,800 alleles · common exomes 574,001/1,458,922 · genomes 62,825/151,878 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	49.4%	2
South Asian	48.2%	2
East Asian	44%	2
Finnishnot grpmax-eligible	39.5%	3
Admixed American	39%	3
European (non-Finnish)	38.7%	3
Remaining individualsnot grpmax-eligible	38.6%	3
Amishnot grpmax-eligible	28.4%	4
Middle Eastern	26.8%	4
Ashkenazi Jewishnot grpmax-eligible	21.6%	5

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: KAT2B
Protein: p.Glu103=
Coding: c.309G>A
MANE Select: NM_003884
dbSNP: rs3021408
Type: single nucleotide variant
Location: chr3:20072338 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.22 · 25 PDB

Full KAT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT2B p.Glu103Lys Uncertain significance ★ ⚠ same residue
KAT2B p.Ile198Val Uncertain significance ★★ ⚠ same type
KAT2B c.1043+115G>A Benign ★★ same type
KAT2B c.1044-72T>C Benign ★★ same type
KAT2B c.1151-47G>T Benign ★★ same type
KAT2B c.1623-40C>G Benign ★★ same type
KAT2B c.1861-37T>C Benign ★★ same type
KAT2B c.1861-98G>T Benign ★★ 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/kat2b-p-glu103 (accessed [today's date]).

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