Is CD81 p.Thr149fs (c.445dup) pathogenic?

CD81 p.Thr149fs (c.445dup) is classified Pathogenic in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). Associated with immunodeficiency, common variable, 6.

What condition is associated with CD81 p.Thr149fs (c.445dup)?

CD81 p.Thr149fs (c.445dup) is associated with immunodeficiency, common variable, 6 (ClinVar).

CD81 p.Thr149fs

c.445dup · VCV4856241

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

immunodeficiency, common variable, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.2	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CD81
Protein: p.Thr149fs
Coding: c.445dup
MANE Select: NM_004356
Type: Duplication
Location: chr11:2395505 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 149: an α-helix

Full CD81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency, common variable, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD81 p.Thr149Ala Uncertain significance ★ ⚠ same residue
CD81 p.Thr149Pro Uncertain significance ★ ⚠ same residue
CD81 p.Asn141Lys Uncertain significance ★★ ⚠ same condition
CD81 p.Asp137Asn Uncertain significance ★★ ⚠ same condition
CD81 p.Asp195Asn Uncertain significance ★★ ⚠ same condition
CD81 c.459+4C>T Benign/Likely benign ★★ same condition
CD81 c.648+10C>T Benign/Likely benign ★★ same condition
CD81 p.Asp138= Benign/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/cd81-p-thr149fs (accessed [today's date]).

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