Is KAT6A p.Ala1908Thr (c.5722G>A) pathogenic?

KAT6A p.Ala1908Thr (c.5722G>A) is classified Conflicting classifications of pathogenicity in KAT6A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-13). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with KAT6A p.Ala1908Thr (c.5722G>A)?

KAT6A p.Ala1908Thr (c.5722G>A) is associated with Inborn genetic diseases (ClinVar).

How common is KAT6A p.Ala1908Thr (c.5722G>A) in the general population?

KAT6A p.Ala1908Thr (c.5722G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about KAT6A p.Ala1908Thr (c.5722G>A)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

KAT6A p.Ala1908Thr

c.5722G>A · rs1359574944 · VCV1358066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.54	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 1.6	GERP -2.5, phastCons 0.89
Regional constraint	o/e 0.87	unconstrained · MANE · 1,300 bp · p 0.0013 · regional, not allelic
Overall
CADD	13.81	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000805% 13/1,614,192 alleles · very rare exomes 13/1,461,890 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
Admixed American	0.00167%	60,030
South Asian	0.0011%	91,082
European (non-Finnish)	0.000763%	131,115

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.Ala1908Thr
Coding: c.5722G>A
MANE Select: NM_006766
dbSNP: rs1359574944
Type: single nucleotide variant
Location: chr8:41932498 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB

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.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
KAT6A p.Asn1898Ser 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-ala1908thr (accessed [today's date]).

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