Is PRKAB2 p.Asp41Val (c.122A>T) pathogenic?

PRKAB2 p.Asp41Val (c.122A>T) is classified Uncertain significance in PRKAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.4816); Absent from gnomAD v4.1.

How common is PRKAB2 p.Asp41Val (c.122A>T) in the general population?

PRKAB2 p.Asp41Val (c.122A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAB2 p.Asp41Val (c.122A>T)?

AlphaMissense predicts ambiguous (score 0.4816) — an in-silico prediction, not a clinical call.

PRKAB2 p.Asp41Val

c.122A>T · VCV3938052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4816 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4816	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -5.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 9,633 bp · p 0.085 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKAB2
Protein: p.Asp41Val
Coding: c.122A>T
MANE Select: NM_005399
Type: single nucleotide variant
Location: chr1:147172023 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 17 PDB
Residue 41: the 'disordered' region

Full PRKAB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAB2 p.Ala28Gly Uncertain significance ★ ⚠ same type
PRKAB2 p.Ala28Ser Uncertain significance ★ ⚠ same type
PRKAB2 p.Arg77Trp Uncertain significance ★ same type
PRKAB2 p.Asn98Ser Uncertain significance ★ ⚠ same type
PRKAB2 p.Asp248Asn Uncertain significance ★ ⚠ same type
PRKAB2 p.Cys178Phe Uncertain significance ★ ⚠ same type
PRKAB2 p.Gln124Pro Uncertain significance ★ ⚠ same type
PRKAB2 p.Glu22Asp 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/prkab2-p-asp41val (accessed [today's date]).

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