Is PRKAB1 p.Lys89Glu (c.265A>G) pathogenic?

PRKAB1 p.Lys89Glu (c.265A>G) is classified Uncertain significance in PRKAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.265); Ultra-rare (popmax 0.0853%, sas).

How common is PRKAB1 p.Lys89Glu (c.265A>G) in the general population?

PRKAB1 p.Lys89Glu (c.265A>G) is ultra-rare (popmax 0.0853%, sas) (gnomAD).

What do computational predictors say about PRKAB1 p.Lys89Glu (c.265A>G)?

AlphaMissense predicts likely benign (score 0.265) — an in-silico prediction, not a clinical call.

PRKAB1 p.Lys89Glu

c.265A>G · VCV4572038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0853%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.265	likely benign
REVEL	0.58	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 12 kb · p 1.8e-06 · regional, not allelic
Overall
CADD	25.2	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 0.0853% South Asian · 77/90,264 alleles

Filtering AF 0.0699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0643%

Overall 0.00814% 131/1,610,242 alleles · ultra-rare exomes 127/1,457,932 · genomes 4/152,310 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0853%	1,172
Remaining individualsnot grpmax-eligible	0.0112%	8,907
European (non-Finnish)	0.00373%	26,777
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560
Finnishnot grpmax-eligible	0.00313%	31,992

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: PRKAB1
Protein: p.Lys89Glu
Coding: c.265A>G
MANE Select: NM_006253
Type: single nucleotide variant
Location: chr12:119672406 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.16 · 12 PDB
Residue 89: the 'glycogen-binding domain' region

Full PRKAB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAB1 p.Ala75Ser Uncertain significance ★ ⚠ same type
PRKAB1 p.Arg201Pro Uncertain significance ★ ⚠ same type
PRKAB1 p.Arg78Gln Uncertain significance ★ ⚠ same type
PRKAB1 p.Arg83Gln Uncertain significance ★ ⚠ same type
PRKAB1 p.Asp175Asn Uncertain significance ★ ⚠ same type
PRKAB1 p.Asp71His Uncertain significance ★ ⚠ same type
PRKAB1 p.Gln64Glu Uncertain significance ★ ⚠ same type
PRKAB1 p.Glu197Lys Uncertain significance ★ ⚠ 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/prkab1-p-lys89glu (accessed [today's date]).

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