Is CD81 p.Asp138= (c.414T>C) pathogenic?

CD81 p.Asp138= (c.414T>C) is classified Benign/Likely benign in CD81 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.337%, nfe); Associated with immunodeficiency, common variable, 6.

What condition is associated with CD81 p.Asp138= (c.414T>C)?

CD81 p.Asp138= (c.414T>C) is associated with immunodeficiency, common variable, 6 (ClinVar).

How common is CD81 p.Asp138= (c.414T>C) in the general population?

CD81 p.Asp138= (c.414T>C) is rare (popmax 0.337%, nfe) (gnomAD).

CD81 p.Asp138=

c.414T>C · rs143644902 · VCV439472

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.337%, nfe)

Conditions

immunodeficiency, common variable, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -2.9
Overall
CADD	0.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.337% European (non-Finnish) · 3,973/1,179,894 alleles

Filtering AF 0.328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.324%

Overall 0.273% 4,399/1,612,744 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.337%	297
Finnishnot grpmax-eligible	0.311%	322
Remaining individualsnot grpmax-eligible	0.197%	508
Admixed American	0.085%	1,177
African / African-American	0.036%	2,779
South Asian	0.0252%	3,961
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,227

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: CD81
Protein: p.Asp138=
Coding: c.414T>C
MANE Select: NM_004356
dbSNP: rs143644902
Type: single nucleotide variant
Location: chr11:2395475 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB

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.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.Pro53= Likely benign ★★ same condition
CD81 p.Ser199= Benign ★★ same condition
CD81 c.182-5G>A Conflicting classifications of pathogenicity ★ 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-asp138 (accessed [today's date]).

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