Is KAT5 p.Glu3Asp (c.9G>C) pathogenic?

KAT5 p.Glu3Asp (c.9G>C) is classified Uncertain significance in KAT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely benign (0.0773); Ultra-rare (popmax 0.022%, sas); Associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities.

How common is KAT5 p.Glu3Asp (c.9G>C) in the general population?

KAT5 p.Glu3Asp (c.9G>C) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about KAT5 p.Glu3Asp (c.9G>C)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

KAT5 p.Glu3Asp

Q: What condition is associated with KAT5 p.Glu3Asp (c.9G>C)?

KAT5 p.Glu3Asp (c.9G>C) is associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (ClinVar).

c.9G>C · VCV3341412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.98	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 544 bp · p 0.75 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.022% South Asian · 14/63,752 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00105% 15/1,425,496 alleles · ultra-rare exomes 15/1,273,134 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,554
Remaining individualsnot grpmax-eligible	0.00184%	54,358

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: KAT5
Protein: p.Glu3Asp
Coding: c.9G>C
MANE Select: NM_182710
Type: single nucleotide variant
Location: chr11:65712276 (GRCh38)
Gene constraint: LOEUF 0.594 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 76.76 · 3 PDB

Full KAT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT5 p.Cys308Ser Uncertain significance ★★ same condition
KAT5 p.Gln310His Uncertain significance ★★ ⚠ same condition
KAT5 p.Ser223Leu Uncertain significance ★★ ⚠ same condition
KAT5 p.Thr180Met Uncertain significance ★★ ⚠ same condition
KAT5 p.Arg86Cys Likely pathogenic ★ same condition
KAT5 c.690+7C>T Uncertain significance ★ same condition
KAT5 p.Ala401Thr Uncertain significance ★ ⚠ same condition
KAT5 p.Arg120Leu 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/kat5-p-glu3asp (accessed [today's date]).

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