Is KAT2B p.Pro507Ser (c.1519C>T) pathogenic?

KAT2B p.Pro507Ser (c.1519C>T) is classified Uncertain significance in KAT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: ambiguous (0.3961); Rare (popmax 0.164%, mid).

How common is KAT2B p.Pro507Ser (c.1519C>T) in the general population?

KAT2B p.Pro507Ser (c.1519C>T) is rare (popmax 0.164%, mid) (gnomAD).

What do computational predictors say about KAT2B p.Pro507Ser (c.1519C>T)?

AlphaMissense predicts ambiguous (score 0.3961) — an in-silico prediction, not a clinical call.

KAT2B p.Pro507Ser

c.1519C>T · VCV3531829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3961 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3961	ambiguous
REVEL	0.168	moderately benign-leaning
SaProt	LLR -1.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 0.0084 · regional, not allelic
Overall
CADD	23.6	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 0.164% Middle Eastern · 10/6,084 alleles

Filtering AF 0.0891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0678%

Overall 0.00818% 132/1,613,994 alleles · rare exomes 122/1,461,860 · genomes 10/152,134 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.164%	608
Admixed American	0.0117%	8,571
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)	0.00907%	11,028
African / African-American	0.00134%	74,900

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.Pro507Ser
Coding: c.1519C>T
MANE Select: NM_003884
Type: single nucleotide variant
Location: chr3:20126010 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.22 · 25 PDB
Residue 507: the n-acetyltransferase domain

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

Similar variants

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
KAT2B c.2004+48C>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-pro507ser (accessed [today's date]).

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