Is KAT8 p.Ala11Val (c.32C>T) pathogenic?

KAT8 p.Ala11Val (c.32C>T) is classified Uncertain significance in KAT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-21). AlphaMissense: likely benign (0.1346); Very rare (popmax 0.00469%, sas).

How common is KAT8 p.Ala11Val (c.32C>T) in the general population?

KAT8 p.Ala11Val (c.32C>T) is very rare (popmax 0.00469%, sas) (gnomAD).

What do computational predictors say about KAT8 p.Ala11Val (c.32C>T)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

KAT8 p.Ala11Val

c.32C>T · rs901263157 · VCV1703415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00469%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 139 bp · p 0.14 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 0.00469% South Asian · 3/64,018 alleles

Filtering AF 0.00124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000645%

Overall 0.000719% 10/1,391,276 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00469%	21,339
European (non-Finnish)	0.000656%	152,550

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: KAT8
Protein: p.Ala11Val
Coding: c.32C>T
MANE Select: NM_032188
dbSNP: rs901263157
Type: single nucleotide variant
Location: chr16:31117713 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 44 PDB
Residue 11: the 'disordered' region

Full KAT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT8 p.Tyr90Cys Likely pathogenic ★★ same type
KAT8 p.Arg144His Uncertain significance ★★ ⚠ same type
KAT8 p.Gly19Arg Uncertain significance ★★ ⚠ same type
KAT8 p.Ile57Val Uncertain significance ★★ ⚠ same type
KAT8 p.Lys203Ter Uncertain significance ★★ same type
KAT8 p.Leu370= Benign ★★ same type
KAT8 p.Pro352= Benign ★★ same type
KAT8 p.Arg108Trp 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/kat8-p-ala11val (accessed [today's date]).

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