Is KAT8 p.Ala172= (c.516G>A) pathogenic?

KAT8 p.Ala172= (c.516G>A) is classified Likely benign in KAT8 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-02-15). Ultra-rare (popmax 0.0346%, afr); Associated with Inborn genetic diseases.

What condition is associated with KAT8 p.Ala172= (c.516G>A)?

KAT8 p.Ala172= (c.516G>A) is associated with Inborn genetic diseases (ClinVar).

How common is KAT8 p.Ala172= (c.516G>A) in the general population?

KAT8 p.Ala172= (c.516G>A) is ultra-rare (popmax 0.0346%, afr) (gnomAD).

KAT8 p.Ala172=

c.516G>A · rs150400146 · VCV2342354

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.047, phastCons 1
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0346% African / African-American · 26/75,048 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00285% 46/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0346%	2,886
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.0011%	90,770
South Asian	0.0011%	91,076

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.Ala172=
Coding: c.516G>A
MANE Select: NM_032188
dbSNP: rs150400146
Type: single nucleotide variant
Location: chr16:31127088 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 44 PDB

Full KAT8 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

KAT8 p.Tyr90Cys Likely pathogenic ★★ same condition
KAT8 p.Arg144His Uncertain significance ★★ ⚠ same condition
KAT8 p.Arg140Cys Pathogenic ★ same condition
KAT8 c.1312+12G>A Uncertain significance ★ same condition
KAT8 c.1312+16C>G Uncertain significance ★ same condition
KAT8 c.1312+25G>C Uncertain significance ★ same condition
KAT8 c.1312+31G>A Uncertain significance ★ same condition
KAT8 c.1312+58G>A 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/kat8-p-ala172 (accessed [today's date]).

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