Is B2M p.Ala11Pro (c.31G>C) pathogenic?

B2M p.Ala11Pro (c.31G>C) is classified Uncertain significance in B2M (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-22). AlphaMissense: ambiguous (0.5134); Very rare (popmax 0.000593%, nfe); Associated with hypoproteinemia, hypercatabolic.

What condition is associated with B2M p.Ala11Pro (c.31G>C)?

B2M p.Ala11Pro (c.31G>C) is associated with hypoproteinemia, hypercatabolic (ClinVar).

How common is B2M p.Ala11Pro (c.31G>C) in the general population?

B2M p.Ala11Pro (c.31G>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about B2M p.Ala11Pro (c.31G>C)?

AlphaMissense predicts ambiguous (score 0.5134) — an in-silico prediction, not a clinical call.

B2M p.Ala11Pro

c.31G>C · rs104894481 · VCV17740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

hypoproteinemia, hypercatabolic

Computational evidence

Protein change
AlphaMissense	0.5134	ambiguous
REVEL	0.312	indeterminate
SaProt	LLR -14.31	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -1.3, phastCons 0.94
Overall
CADD	14.79	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 0.000593% European (non-Finnish) · 7/1,180,022 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,940 alleles · very rare exomes 7/1,461,654 · genomes 0/152,286 · joint denominator

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.Ala11Pro
Coding: c.31G>C
MANE Select: NM_004048
dbSNP: rs104894481
Type: single nucleotide variant
Location: chr15:44711577 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1396 PDB
Residue 11: a UniProt-annotated variant site (in imd43; lower levels of b2m, mhc class i and fcgrt proteins)

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.Ala11Val Uncertain significance ★ ⚠ same residue
B2M p.Ala11= Likely benign ★ same residue
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

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-ala11pro (accessed [today's date]).

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