Is KAT6A p.Met2002Val (c.6004A>G) pathogenic?

KAT6A p.Met2002Val (c.6004A>G) is classified Likely benign in KAT6A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.3002); Ultra-rare (popmax 0.0169%, mid); Associated with Inborn genetic diseases.

What condition is associated with KAT6A p.Met2002Val (c.6004A>G)?

KAT6A p.Met2002Val (c.6004A>G) is associated with Inborn genetic diseases (ClinVar).

How common is KAT6A p.Met2002Val (c.6004A>G) in the general population?

KAT6A p.Met2002Val (c.6004A>G) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about KAT6A p.Met2002Val (c.6004A>G)?

AlphaMissense predicts likely benign (score 0.3002) — an in-silico prediction, not a clinical call.

KAT6A p.Met2002Val

c.6004A>G · rs777771800 · VCV1991189

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3002	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,300 bp · p 0.0013 · regional, not allelic
Overall
CADD	22.6	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 0.0169% Middle Eastern · 1/5,918 alleles

Filtering AF 0.00978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00783%

Overall 0.00284% 45/1,585,136 alleles · ultra-rare exomes 39/1,432,926 · genomes 6/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,918
South Asian	0.0162%	6,169
African / African-American	0.0122%	8,204
Remaining individualsnot grpmax-eligible	0.00491%	20,382
East Asian	0.00225%	44,518
European (non-Finnish)	0.00146%	68,571

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: KAT6A
Protein: p.Met2002Val
Coding: c.6004A>G
MANE Select: NM_006766
dbSNP: rs777771800
Type: single nucleotide variant
Location: chr8:41932216 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB

Full KAT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6A p.Arg1129Ter Pathogenic ★★ same condition
KAT6A p.Arg148Ter Pathogenic ★★ same condition
KAT6A p.Arg286Ter Pathogenic ★★ same condition
KAT6A p.Arg735Ter Pathogenic ★★ same condition
KAT6A p.Ala1451Gly Uncertain significance ★★ ⚠ same condition
KAT6A p.Ala492Val Uncertain significance ★★ ⚠ same condition
KAT6A p.Arg1086Ser Uncertain significance ★★ ⚠ same condition
KAT6A p.Asn1898Ser 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/kat6a-p-met2002val (accessed [today's date]).

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