Is CD81 p.Ser199= (c.597C>T) pathogenic?

CD81 p.Ser199= (c.597C>T) is classified Benign in CD81 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 23.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency, common variable, 6.

What condition is associated with CD81 p.Ser199= (c.597C>T)?

CD81 p.Ser199= (c.597C>T) is associated with immunodeficiency, common variable, 6 (ClinVar).

CD81 p.Ser199=

Q: How common is CD81 p.Ser199= (c.597C>T) in the general population?

CD81 p.Ser199= (c.597C>T) is common (popmax 23.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.597C>T · rs14077 · VCV810931

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 23.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency, common variable, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.005	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.5	GERP -3.7
Overall
CADD	8.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.4% African / African-American · 17,576/75,010 alleles

Filtering AF 23.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 23%

Overall 2.18% 35,102/1,611,752 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	23.4%	4
Middle Eastern	4.84%	21
Ashkenazi Jewishnot grpmax-eligible	4.28%	23
South Asian	3.38%	30
Remaining individualsnot grpmax-eligible	3.23%	31
Admixed American	3.13%	32
East Asian	2.56%	39
Amishnot grpmax-eligible	1.43%	70
European (non-Finnish)	0.661%	151
Finnishnot grpmax-eligible	0.0518%	1,929

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.Ser199=
Coding: c.597C>T
MANE Select: NM_004356
dbSNP: rs14077
Type: single nucleotide variant
Location: chr11:2396663 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 199: 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.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.Pro53= Likely 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-ser199 (accessed [today's date]).

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