Is KAT6A p.Pro85Ser (c.253C>T) pathogenic?

KAT6A p.Pro85Ser (c.253C>T) is classified Likely benign in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.1508); Ultra-rare (popmax 0.0362%, sas); Associated with Inborn genetic diseases.

What condition is associated with KAT6A p.Pro85Ser (c.253C>T)?

KAT6A p.Pro85Ser (c.253C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KAT6A p.Pro85Ser (c.253C>T) in the general population?

KAT6A p.Pro85Ser (c.253C>T) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about KAT6A p.Pro85Ser (c.253C>T)?

AlphaMissense predicts likely benign (score 0.1508) — an in-silico prediction, not a clinical call.

KAT6A p.Pro85Ser

c.253C>T · VCV4622451

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1508	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.96 · regional, not allelic
Overall
CADD	24.5	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 0.0362% South Asian · 33/91,092 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00211% 34/1,614,044 alleles · ultra-rare exomes 33/1,461,888 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro85Ser
Coding: c.253C>T
MANE Select: NM_006766
Type: single nucleotide variant
Location: chr8:42048725 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 85: the 'required for activation of runx1-1' region; the 'required for nuclear localization' region

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.Pro85Leu Uncertain significance ★ ⚠ same residue
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

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-pro85ser (accessed [today's date]).

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