Is KAT6A p.Arg486His (c.1457G>A) pathogenic?

KAT6A p.Arg486His (c.1457G>A) is classified Likely benign in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-07). AlphaMissense: likely benign (0.1139); Very rare (popmax 0.00224%, eas).

How common is KAT6A p.Arg486His (c.1457G>A) in the general population?

KAT6A p.Arg486His (c.1457G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about KAT6A p.Arg486His (c.1457G>A)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

KAT6A p.Arg486His

c.1457G>A · rs750873194 · VCV2882620

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -8.98	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 23 kb · p 0.54 · regional, not allelic
Overall
CADD	28.8	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 0.00224% East Asian · 1/44,648 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000832%

Overall 0.00143% 23/1,608,614 alleles · very rare exomes 20/1,456,436 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,648
South Asian	0.00222%	45,083
European (non-Finnish)	0.00161%	61,951
African / African-American	0.00134%	74,678

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.Arg486His
Coding: c.1457G>A
MANE Select: NM_006766
dbSNP: rs750873194
Type: single nucleotide variant
Location: chr8:41974729 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 486: the 'interaction with runx1-1' region; the 'interaction with pml' region

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

Similar variants

KAT6A p.Arg486Cys Likely benign ★ ⚠ same residue
KAT6A c.3353-1G>A Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1012Ter Pathogenic ★★ same type
KAT6A p.Arg1019Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1024Ter Pathogenic ★★ same type
KAT6A p.Arg1129Ter Pathogenic ★★ same type
KAT6A p.Arg148Ter Pathogenic ★★ same type
KAT6A p.Arg220Ter Pathogenic/Likely pathogenic ★★ 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/kat6a-p-arg486his (accessed [today's date]).

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