Is CD81 p.Pro53= (c.159C>T) pathogenic?

CD81 p.Pro53= (c.159C>T) is classified Likely benign in CD81 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0493%, mid); Associated with immunodeficiency, common variable, 6.

What condition is associated with CD81 p.Pro53= (c.159C>T)?

CD81 p.Pro53= (c.159C>T) is associated with immunodeficiency, common variable, 6 (ClinVar).

How common is CD81 p.Pro53= (c.159C>T) in the general population?

CD81 p.Pro53= (c.159C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

CD81 p.Pro53=

c.159C>T · rs200365372 · VCV1645740

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

immunodeficiency, common variable, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.19	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -3.6
Overall
CADD	0.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0251%

Overall 0.0257% 414/1,612,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.0401%	2,494
European (non-Finnish)	0.0286%	3,501
South Asian	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Admixed American	0.015%	6,668
African / African-American	0.00534%	18,736
Finnishnot grpmax-eligible	0.00159%	62,876

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.Pro53=
Coding: c.159C>T
MANE Select: NM_004356
dbSNP: rs200365372
Type: single nucleotide variant
Location: chr11:2390504 (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.Asp138= Benign/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-pro53 (accessed [today's date]).

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