Is KAT6B p.Ser141Arg (c.423C>G) pathogenic?

KAT6B p.Ser141Arg (c.423C>G) is classified Conflicting classifications of pathogenicity in KAT6B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2477); Absent from gnomAD v4.1; Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Ser141Arg (c.423C>G)?

KAT6B p.Ser141Arg (c.423C>G) is associated with genitopatellar syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type (ClinVar).

How common is KAT6B p.Ser141Arg (c.423C>G) in the general population?

KAT6B p.Ser141Arg (c.423C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6B p.Ser141Arg (c.423C>G)?

AlphaMissense predicts likely benign (score 0.2477) — an in-silico prediction, not a clinical call.

KAT6B p.Ser141Arg

c.423C>G · rs779662050 · VCV2062013

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.2477	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -7.28	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 0.83	GERP -0.65, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 117 kb · p 0.00012 · regional, not allelic
Overall
CADD	20.6	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

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.Ser141Arg
Coding: c.423C>G
MANE Select: NM_012330
dbSNP: rs779662050
Type: single nucleotide variant
Location: chr10:74843280 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 141: the h15 domain; an α-helix

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.Ser141Asn Uncertain significance ★ ⚠ 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-ser141arg (accessed [today's date]).

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