Is B2M p.Val47= (c.141G>A) pathogenic?

B2M p.Val47= (c.141G>A) is classified Likely benign in B2M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 0.00333%, amr); Associated with hypoproteinemia, hypercatabolic.

What condition is associated with B2M p.Val47= (c.141G>A)?

B2M p.Val47= (c.141G>A) is associated with hypoproteinemia, hypercatabolic (ClinVar).

How common is B2M p.Val47= (c.141G>A) in the general population?

B2M p.Val47= (c.141G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

B2M p.Val47=

c.141G>A · VCV3625617

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

hypoproteinemia, hypercatabolic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.7	GERP -3.7
Overall
CADD	1.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,614,046 alleles · very rare exomes 4/1,461,860 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
European (non-Finnish)	0.000254%	393,345

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: B2M
Protein: p.Val47=
Coding: c.141G>A
MANE Select: NM_004048
Type: single nucleotide variant
Location: chr15:44715496 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1396 PDB
Residue 47: a β-strand; the ig-like c1-type domain

Full B2M gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoproteinemia, hypercatabolic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B2M p.Asp54Asn Uncertain significance ★★ ⚠ same condition
B2M p.Ile55Thr Uncertain significance ★★ ⚠ same condition
B2M p.Lys114Gln Uncertain significance ★★ ⚠ same condition
B2M p.Lys68Glu Uncertain significance ★★ ⚠ same condition
B2M p.Pro92Leu Uncertain significance ★★ ⚠ same condition
B2M c.67+12C>T Likely benign ★★ same condition
B2M c.67+19C>T Benign/Likely benign ★★ same condition
B2M c.68-13C>T Likely benign ★★ 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/b2m-p-val47 (accessed [today's date]).

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