Is KAT2B p.Ala73Val (c.218C>T) pathogenic?

KAT2B p.Ala73Val (c.218C>T) is classified Uncertain significance in KAT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.2382); Ultra-rare (popmax 0.0824%, afr).

How common is KAT2B p.Ala73Val (c.218C>T) in the general population?

KAT2B p.Ala73Val (c.218C>T) is ultra-rare (popmax 0.0824%, afr) (gnomAD).

What do computational predictors say about KAT2B p.Ala73Val (c.218C>T)?

AlphaMissense predicts likely benign (score 0.2382) — an in-silico prediction, not a clinical call.

KAT2B p.Ala73Val

c.218C>T · rs371548043 · VCV2592150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2382	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -7.41	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 6.6	GERP 0.31, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 32 kb · p 0.32 · regional, not allelic
Overall
CADD	25.2	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 0.0824% African / African-American · 59/71,608 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0594%

Overall 0.00494% 78/1,578,240 alleles · ultra-rare exomes 40/1,426,210 · genomes 38/152,030 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0824%	1,214
Middle Eastern	0.0347%	2,886
Remaining individualsnot grpmax-eligible	0.00984%	10,167
East Asian	0.00249%	40,236
Admixed American	0.00175%	57,276
European (non-Finnish)	0.000771%	129,648

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.Ala73Val
Coding: c.218C>T
MANE Select: NM_003884
dbSNP: rs371548043
Type: single nucleotide variant
Location: chr3:20040695 (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.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-ala73val (accessed [today's date]).

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