Is B2M p.His71Arg (c.212A>G) pathogenic?

B2M p.His71Arg (c.212A>G) is classified Uncertain significance in B2M (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely benign (0.102); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with B2M p.His71Arg (c.212A>G)?

B2M p.His71Arg (c.212A>G) is associated with Inborn genetic diseases (ClinVar).

How common is B2M p.His71Arg (c.212A>G) in the general population?

B2M p.His71Arg (c.212A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about B2M p.His71Arg (c.212A>G)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

B2M p.His71Arg

c.212A>G · rs775706574 · VCV2540393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -7.46	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 -1.4	GERP -3.7
Overall
CADD	3.049	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 0.00223% East Asian · 1/44,890 alleles

Overall 6.84e-05% 1/1,461,888 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.His71Arg
Coding: c.212A>G
MANE Select: NM_004048
dbSNP: rs775706574
Type: single nucleotide variant
Location: chr15:44715567 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1396 PDB
Residue 71: a disulfide bond; 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

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.Lys39Glu 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-his71arg (accessed [today's date]).

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