Is B2M p.Lys39Glu (c.115A>G) pathogenic?

B2M p.Lys39Glu (c.115A>G) is classified Uncertain significance in B2M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.2476); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with B2M p.Lys39Glu (c.115A>G)?

B2M p.Lys39Glu (c.115A>G) is associated with Inborn genetic diseases (ClinVar).

How common is B2M p.Lys39Glu (c.115A>G) in the general population?

B2M p.Lys39Glu (c.115A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about B2M p.Lys39Glu (c.115A>G)?

AlphaMissense predicts likely benign (score 0.2476) — an in-silico prediction, not a clinical call.

B2M p.Lys39Glu

c.115A>G · rs2506043131 · VCV3132524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2476 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2476	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.88	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 7.8	GERP 1.9, phastCons 1
Overall
CADD	23.4	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

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: B2M
Protein: p.Lys39Glu
Coding: c.115A>G
MANE Select: NM_004048
dbSNP: rs2506043131
Type: single nucleotide variant
Location: chr15:44715470 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1396 PDB
Residue 39: the ig-like c1-type domain

Full B2M 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

B2M p.Lys68Glu Uncertain significance ★★ ⚠ same condition
B2M p.Pro92Leu Uncertain significance ★★ ⚠ same condition
B2M p.His71Arg Uncertain significance ★ ⚠ same condition
B2M p.Asp54Asn Uncertain significance ★★ ⚠ same type
B2M p.Ile55Thr Uncertain significance ★★ ⚠ same type
B2M p.Lys114Gln Uncertain significance ★★ ⚠ same type
B2M c.67+12C>T Likely benign ★★ same type
B2M c.67+19C>T Benign/Likely benign ★★ 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/b2m-p-lys39glu (accessed [today's date]).

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