Is KAT5 p.Cys308Ser (c.922T>A) pathogenic?

KAT5 p.Cys308Ser (c.922T>A) is classified Uncertain significance in KAT5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). AlphaMissense: ambiguous (0.3909); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities.

How common is KAT5 p.Cys308Ser (c.922T>A) in the general population?

KAT5 p.Cys308Ser (c.922T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT5 p.Cys308Ser (c.922T>A)?

AlphaMissense predicts ambiguous (score 0.3909) — an in-silico prediction, not a clinical call.

KAT5 p.Cys308Ser

Q: What condition is associated with KAT5 p.Cys308Ser (c.922T>A)?

KAT5 p.Cys308Ser (c.922T>A) is associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (ClinVar).

c.922T>A · rs892470790 · VCV2431820

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.3909	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -3.69	tolerated
Splicing
SpliceAI	Δ0.25	donor loss, 20 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 5,370 bp · p 3e-25 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C275S vs ClinVar C308S) — verify the residue.

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: KAT5
Protein: p.Cys308Ser
Coding: c.922T>A
MANE Select: NM_182710
dbSNP: rs892470790
Type: single nucleotide variant
Location: chr11:65714726 (GRCh38)
Gene constraint: LOEUF 0.594 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 76.76 · 3 PDB
Residue 275 UniProt numbering: the myst-type hat domain; an α-helix

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.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
KAT5 p.Arg304Cys 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-cys308ser (accessed [today's date]).

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