Is KAT6B p.Arg960Gln (c.2879G>A) pathogenic?

KAT6B p.Arg960Gln (c.2879G>A) is classified Conflicting classifications of pathogenicity in KAT6B (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-23). AlphaMissense: ambiguous (0.3674); Ultra-rare (popmax 0.0165%, mid); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Arg960Gln (c.2879G>A)?

KAT6B p.Arg960Gln (c.2879G>A) is associated with genitopatellar syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Arg960Gln (c.2879G>A) in the general population?

KAT6B p.Arg960Gln (c.2879G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about KAT6B p.Arg960Gln (c.2879G>A)?

AlphaMissense predicts ambiguous (score 0.3674) — an in-silico prediction, not a clinical call.

KAT6B p.Arg960Gln

c.2879G>A · rs753695521 · VCV1017130

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.3674	ambiguous
REVEL	0.671	pathogenic-leaning
SaProt	LLR -7.46	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,071 bp · p 8e-06 · regional, not allelic
Overall
CADD	27.7	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000744% 12/1,613,974 alleles · ultra-rare exomes 10/1,461,720 · genomes 2/152,254 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00549%	18,213
African / African-American	0.00267%	37,508
European (non-Finnish)	0.000339%	294,972

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.Arg960Gln
Coding: c.2879G>A
MANE Select: NM_012330
dbSNP: rs753695521
Type: single nucleotide variant
Location: chr10:75021143 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 960: the 'catalytic' region; the 'interaction with brpf1' region; the myst-type hat domain

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

Also linked: blepharophimosis - intellectual disability syndrome, SBBYS type

Similar variants

KAT6B p.Arg960Trp Benign/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.Arg783Ter Pathogenic/Likely pathogenic ★★ same condition
KAT6B p.Gln1014Ter Pathogenic ★★ same condition
KAT6B p.Gln1752Ter Pathogenic ★★ same condition
KAT6B p.Gln1768Ter Pathogenic ★★ 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-arg960gln (accessed [today's date]).

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