Is KAT6B p.Ser1998Pro (c.5992T>C) pathogenic?

KAT6B p.Ser1998Pro (c.5992T>C) is classified Likely benign in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.2335); Ultra-rare (popmax 0.025%, amr); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Ser1998Pro (c.5992T>C)?

KAT6B p.Ser1998Pro (c.5992T>C) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Ser1998Pro (c.5992T>C) in the general population?

KAT6B p.Ser1998Pro (c.5992T>C) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about KAT6B p.Ser1998Pro (c.5992T>C)?

AlphaMissense predicts likely benign (score 0.2335) — an in-silico prediction, not a clinical call.

KAT6B p.Ser1998Pro

c.5992T>C · rs761909075 · VCV2748565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2335 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

genitopatellar syndrome

Computational evidence

Protein change
AlphaMissense	0.2335	likely benign
REVEL	0.417	indeterminate
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 979 bp · p 0.00018 · regional, not allelic
Overall
CADD	23.8	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 0.025% Admixed American · 15/60,006 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.000929% 15/1,614,026 alleles · ultra-rare exomes 13/1,461,878 · genomes 2/152,148 · joint denominator

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.Ser1998Pro
Coding: c.5992T>C
MANE Select: NM_012330
dbSNP: rs761909075
Type: single nucleotide variant
Location: chr10:75030816 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1998: 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 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
KAT6B p.Ala1317Thr Uncertain significance ★★ ⚠ same condition
KAT6B p.Ala1498Ser 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-ser1998pro (accessed [today's date]).

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