Is KAT6B p.Val1663Ile (c.4987G>A) pathogenic?

KAT6B p.Val1663Ile (c.4987G>A) is classified Conflicting classifications of pathogenicity in KAT6B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.3434); Very rare (popmax 0.00223%, eas); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Val1663Ile (c.4987G>A)?

KAT6B p.Val1663Ile (c.4987G>A) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Val1663Ile (c.4987G>A) in the general population?

KAT6B p.Val1663Ile (c.4987G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about KAT6B p.Val1663Ile (c.4987G>A)?

AlphaMissense predicts ambiguous (score 0.3434) — an in-silico prediction, not a clinical call.

KAT6B p.Val1663Ile

c.4987G>A · rs777433819 · VCV561958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3434 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.3434	ambiguous
REVEL	0.409	indeterminate
SaProt	LLR -6.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 394 bp · p 5e-10 · regional, not allelic
Overall
CADD	25.1	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
African / African-American	0.00133%	74,916
European (non-Finnish)	0.00127%	78,670
South Asian	0.0011%	91,090

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: KAT6B
Protein: p.Val1663Ile
Coding: c.4987G>A
MANE Select: NM_012330
dbSNP: rs777433819
Type: single nucleotide variant
Location: chr10:75029811 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1663: the 'interaction with runx1 and runx2' region

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

Disease context

genitopatellar syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6B p.Val1663Leu Uncertain significance ★ ⚠ same residue
KAT6B p.Val1663= Likely benign ★ same residue
KAT6B c.3664+1G>A Pathogenic ★★ same condition
KAT6B p.Arg1058Ter Pathogenic ★★ same condition
KAT6B p.Arg1797Ter Pathogenic ★★ same condition
KAT6B p.Gln1752Ter Pathogenic ★★ same condition
KAT6B c.2373+6C>A Uncertain significance ★★ same condition
KAT6B c.2374-3T>C Uncertain significance ★★ same condition

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-val1663ile (accessed [today's date]).

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