Is CD70 p.Arg179Ter (c.535C>T) pathogenic?

CD70 p.Arg179Ter (c.535C>T) is classified Pathogenic in CD70 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-10). Very rare (popmax 0.000339%, nfe); Associated with severe combined immunodeficiency due to CD70 deficiency.

What condition is associated with CD70 p.Arg179Ter (c.535C>T)?

CD70 p.Arg179Ter (c.535C>T) is associated with severe combined immunodeficiency due to CD70 deficiency (ClinVar).

How common is CD70 p.Arg179Ter (c.535C>T) in the general population?

CD70 p.Arg179Ter (c.535C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

CD70 p.Arg179Ter

Q: How is EBV-induced lymphoproliferative disease due to CD70 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.535C>T · rs368303189 · VCV599337

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

severe combined immunodeficiency due to CD70 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -3, phastCons 0.008
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,902 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,720 alleles · very rare

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: CD70
Protein: p.Arg179Ter
Coding: c.535C>T
MANE Select: NM_001252
dbSNP: rs368303189
Type: single nucleotide variant
Location: chr19:6586067 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 179: a UniProt-annotated variant site (in lpfs3; loss of protein expression); the thd domain

Full CD70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency due to CD70 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For EBV-induced lymphoproliferative disease due to CD70 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CD70 p.Phe186del Pathogenic same condition
CD70 p.Ser84fs Pathogenic same condition
CD70 p.Leu23Phe Uncertain significance ★★ ⚠ same type
CD70 p.Ser146Ile Uncertain significance ★★ same type
CD70 p.Ser9Leu Uncertain significance ★★ ⚠ same type
CD70 p.Thr118Met Uncertain significance ★★ ⚠ same type
CD70 p.Thr119Met Uncertain significance ★★ ⚠ same type
CD70 p.Val130Met Uncertain significance ★★ ⚠ same type

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/cd70-p-arg179ter (accessed [today's date]).

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