Is KAT2A p.Arg17Trp (c.49C>T) pathogenic?

KAT2A p.Arg17Trp (c.49C>T) is classified Uncertain significance in KAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely benign (0.257); Absent from gnomAD v4.1.

How common is KAT2A p.Arg17Trp (c.49C>T) in the general population?

KAT2A p.Arg17Trp (c.49C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT2A p.Arg17Trp (c.49C>T)?

AlphaMissense predicts likely benign (score 0.257) — an in-silico prediction, not a clinical call.

KAT2A p.Arg17Trp

c.49C>T · rs1555667346 · VCV2323152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.257 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,356,260)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.257	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.15	unconstrained · MANE · 252 bp · p 0.09 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,356,260). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KAT2A
Protein: p.Arg17Trp
Coding: c.49C>T
MANE Select: NM_021078
dbSNP: rs1555667346
Type: single nucleotide variant
Location: chr17:42121256 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 15 PDB
Residue 17: the 'disordered' region

Full KAT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT2A c.464-18C>G Benign ★★ same type
KAT2A p.Leu664= Benign ★★ same type
KAT2A p.Leu719= Benign ★★ same type
KAT2A p.Ala274Val Uncertain significance ★ ⚠ same type
KAT2A p.Ala426Val Uncertain significance ★ ⚠ same type
KAT2A p.Ala53Ser Uncertain significance ★ ⚠ same type
KAT2A p.Ala53Val Uncertain significance ★ ⚠ same type
KAT2A p.Arg171Gly 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/kat2a-p-arg17trp (accessed [today's date]).

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