Is KAT7 p.Thr254Met (c.761C>T) pathogenic?

KAT7 p.Thr254Met (c.761C>T) is classified Uncertain significance in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: ambiguous (0.3861); Ultra-rare (popmax 0.0345%, amr).

How common is KAT7 p.Thr254Met (c.761C>T) in the general population?

KAT7 p.Thr254Met (c.761C>T) is ultra-rare (popmax 0.0345%, amr) (gnomAD).

What do computational predictors say about KAT7 p.Thr254Met (c.761C>T)?

AlphaMissense predicts ambiguous (score 0.3861) — an in-silico prediction, not a clinical call.

KAT7 p.Thr254Met

c.761C>T · rs201996993 · VCV2562026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0345%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3861	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -13.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 8,723 bp · p 0.015 · regional, not allelic
Overall
CADD	27.5	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 0.0345% Admixed American · 16/46,384 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0176%

Overall 0.00746% 112/1,501,470 alleles · ultra-rare exomes 89/1,349,318 · genomes 23/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0345%	2,899
Finnishnot grpmax-eligible	0.0289%	3,455
Middle Eastern	0.0175%	5,706
European (non-Finnish)	0.00667%	14,989
Remaining individualsnot grpmax-eligible	0.00347%	28,813
African / African-American	0.00142%	70,368

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: KAT7
Protein: p.Thr254Met
Coding: c.761C>T
MANE Select: NM_007067
dbSNP: rs201996993
Type: single nucleotide variant
Location: chr17:49811483 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.21 · 8 PDB

Full KAT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT7 p.Ala449= Benign ★★ same type
KAT7 c.580+1G>A Uncertain significance ★ same type
KAT7 p.Ala133Val Uncertain significance ★ ⚠ same type
KAT7 p.Ala154Thr Uncertain significance ★ ⚠ same type
KAT7 p.Ala40Thr Uncertain significance ★ ⚠ same type
KAT7 p.Ala8Val Uncertain significance ★ ⚠ same type
KAT7 p.Arg344Leu Uncertain significance ★ ⚠ same type
KAT7 p.Arg37Gln Uncertain significance ★ ⚠ 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/kat7-p-thr254met (accessed [today's date]).

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