Is KAT6A p.Pro970Ser (c.2908C>T) pathogenic?

KAT6A p.Pro970Ser (c.2908C>T) is classified Benign in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.0983); Very rare (popmax 0.004%, afr).

How common is KAT6A p.Pro970Ser (c.2908C>T) in the general population?

KAT6A p.Pro970Ser (c.2908C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about KAT6A p.Pro970Ser (c.2908C>T)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

KAT6A p.Pro970Ser

c.2908C>T · VCV3709575

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.20	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 1.3	GERP -0.37, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 2,019 bp · p 0.081 · regional, not allelic
Overall
CADD	14.49	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 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,090 alleles · very rare exomes 1/1,461,890 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,981
European (non-Finnish)	8.47e-05%	1,180,044

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.Pro970Ser
Coding: c.2908C>T
MANE Select: NM_006766
Type: single nucleotide variant
Location: chr8:41940973 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 970: the 'disordered' region

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

Similar variants

KAT6A p.Pro970= 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-pro970ser (accessed [today's date]).

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