Is KAT5 p.Pro142Leu (c.425C>T) pathogenic?

KAT5 p.Pro142Leu (c.425C>T) is classified Uncertain significance in KAT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). AlphaMissense: ambiguous (0.5512); Very rare (popmax 0.00167%, amr).

How common is KAT5 p.Pro142Leu (c.425C>T) in the general population?

KAT5 p.Pro142Leu (c.425C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KAT5 p.Pro142Leu (c.425C>T)?

AlphaMissense predicts ambiguous (score 0.5512) — an in-silico prediction, not a clinical call.

KAT5 p.Pro142Leu

c.425C>T · rs1479110981 · VCV3233455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5512	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 858 bp · p 0.0036 · regional, not allelic
Overall
CADD	25.0	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 P109L vs ClinVar P142L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,086 alleles · very rare exomes 6/1,461,862 · genomes 0/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.000424%	236,002

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.Pro142Leu
Coding: c.425C>T
MANE Select: NM_182710
dbSNP: rs1479110981
Type: single nucleotide variant
Location: chr11:65713388 (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

Similar variants

KAT5 p.Cys308Ser Uncertain significance ★★ same type
KAT5 p.Gln310His Uncertain significance ★★ ⚠ same type
KAT5 p.Ser223Leu Uncertain significance ★★ ⚠ same type
KAT5 p.Thr180Met Uncertain significance ★★ ⚠ same type
KAT5 p.Val32Asp Uncertain significance ★★ same type
KAT5 p.Gly43= Benign/Likely benign ★★ same type
KAT5 p.Ser66= Benign ★★ same type
KAT5 p.Thr432= Likely benign ★★ same type

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-pro142leu (accessed [today's date]).

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