Is KAT2B p.Pro27Arg (c.80C>G) pathogenic?

KAT2B p.Pro27Arg (c.80C>G) is classified Uncertain significance in KAT2B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1077); Rare (popmax 0.138%, nfe).

How common is KAT2B p.Pro27Arg (c.80C>G) in the general population?

KAT2B p.Pro27Arg (c.80C>G) is rare (popmax 0.138%, nfe) (gnomAD).

What do computational predictors say about KAT2B p.Pro27Arg (c.80C>G)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

KAT2B p.Pro27Arg

c.80C>G · rs1227332251 · VCV2347855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -0.49, phastCons 0.93
Regional constraint	o/e 1.08	unconstrained · MANE · 32 kb · p 0.32 · regional, not allelic
Overall
CADD	17.72	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% European (non-Finnish) · 1,220/882,120 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.121% 1,290/1,063,948 alleles · rare exomes 1,150/917,474 · genomes 140/146,474 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.138%	723
Admixed American	0.137%	732
Remaining individualsnot grpmax-eligible	0.0896%	1,116
African / African-American	0.0187%	5,343
Ashkenazi Jewishnot grpmax-eligible	0.0177%	5,653
East Asian	0.0066%	15,154

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.Pro27Arg
Coding: c.80C>G
MANE Select: NM_003884
dbSNP: rs1227332251
Type: single nucleotide variant
Location: chr3:20040557 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.22 · 25 PDB
Residue 27: the 'disordered' region

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-pro27arg (accessed [today's date]).

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