Is KAT5 p.Arg448Ter (c.1342C>T) pathogenic?

KAT5 p.Arg448Ter (c.1342C>T) is classified Uncertain significance in KAT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-20). Very rare (popmax 0.0011%, sas); Associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities.

How common is KAT5 p.Arg448Ter (c.1342C>T) in the general population?

KAT5 p.Arg448Ter (c.1342C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

KAT5 p.Arg448Ter

Q: What condition is associated with KAT5 p.Arg448Ter (c.1342C>T)?

KAT5 p.Arg448Ter (c.1342C>T) is associated with neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (ClinVar).

c.1342C>T · VCV3891436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 13
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.2	phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.000169%	590,012

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg448Ter
Coding: c.1342C>T
MANE Select: NM_182710
Type: single nucleotide variant
Location: chr11:65718667 (GRCh38)
Gene constraint: LOEUF 0.594 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 76.76 · 3 PDB
Residue 448: the myst-type hat domain; the 'interaction with atf2' region; 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.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-arg448ter (accessed [today's date]).

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