Is B2M p.Ala11Val (c.32C>T) pathogenic?

B2M p.Ala11Val (c.32C>T) is classified Uncertain significance in B2M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-09). AlphaMissense: likely benign (0.1112); Very rare (popmax 0.00167%, amr); Associated with amyloidosis, hereditary systemic 6.

What condition is associated with B2M p.Ala11Val (c.32C>T)?

B2M p.Ala11Val (c.32C>T) is associated with amyloidosis, hereditary systemic 6, hypoproteinemia, hypercatabolic (ClinVar).

How common is B2M p.Ala11Val (c.32C>T) in the general population?

B2M p.Ala11Val (c.32C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Hereditary ATTR amyloidosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about B2M p.Ala11Val (c.32C>T)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

B2M p.Ala11Val

c.32C>T · VCV3577175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyloidosis, hereditary systemic 6

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.62	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 -0.41	GERP -3.7
Overall
CADD	1.128	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 0.00167% Admixed American · 1/60,026 alleles

Overall 6.84e-05% 1/1,461,662 alleles · very rare

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.Ala11Val
Coding: c.32C>T
MANE Select: NM_004048
Type: single nucleotide variant
Location: chr15:44711578 (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

amyloidosis, hereditary systemic 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypoproteinemia, hypercatabolic

For Hereditary ATTR amyloidosis (Orphanet):

Inheritance: Autosomal dominant
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

B2M p.Ala11Pro 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-ala11val (accessed [today's date]).

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