Is KAT6B p.Asp75Val (c.224A>T) pathogenic?

KAT6B p.Asp75Val (c.224A>T) is classified Uncertain significance in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-15). AlphaMissense: likely benign (0.3213); Absent from gnomAD v4.1.

How common is KAT6B p.Asp75Val (c.224A>T) in the general population?

KAT6B p.Asp75Val (c.224A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6B p.Asp75Val (c.224A>T)?

AlphaMissense predicts likely benign (score 0.3213) — an in-silico prediction, not a clinical call.

KAT6B p.Asp75Val

c.224A>T · VCV4848536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3213 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3213	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -2.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 117 kb · p 0.00012 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KAT6B
Protein: p.Asp75Val
Coding: c.224A>T
MANE Select: NM_012330
Type: single nucleotide variant
Location: chr10:74843081 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 75: the samd1-like winged helix (wh) domain; the 'disordered' region

Full KAT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT6B p.Asp75His Uncertain significance ★ same residue
KAT6B c.1061+1G>A Pathogenic/Likely pathogenic ★★ same type
KAT6B c.3664+1G>A Pathogenic ★★ same type
KAT6B p.Arg1002Ter Pathogenic/Likely pathogenic ★★ same type
KAT6B p.Arg1058Ter Pathogenic ★★ same type
KAT6B p.Arg1797Ter Pathogenic ★★ same type
KAT6B p.Arg352Ter Pathogenic ★★ same type
KAT6B p.Arg783Ter Pathogenic/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/kat6b-p-asp75val (accessed [today's date]).

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