Is B2M c.67+9C>T pathogenic?

B2M c.67+9C>T is classified Likely benign in B2M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). Very rare (popmax 0.00333%, amr); Associated with hypoproteinemia, hypercatabolic.

What condition is associated with B2M c.67+9C>T?

B2M c.67+9C>T is associated with hypoproteinemia, hypercatabolic (ClinVar).

How common is B2M c.67+9C>T in the general population?

B2M c.67+9C>T is very rare (popmax 0.00333%, amr) (gnomAD).

B2M c.67+9C>T

VCV3617749

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
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.081	GERP 0.73
Non-coding constraint	Z 3.00	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	11.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,028 alleles

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

Overall 0.000206% 3/1,459,458 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,014
European (non-Finnish)	8.49e-05%	1,178,392

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
Coding: c.67+9C>T
MANE Select: NM_004048
Type: single nucleotide variant
Location: chr15:44711622 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1396 PDB

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-c-67-plus-9c-t (accessed [today's date]).

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