Is CD96 p.Trp179fs (c.537del) pathogenic?

CD96 p.Trp179fs (c.537del) is classified Likely pathogenic in CD96 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-11-05). Associated with C syndrome.

What condition is associated with CD96 p.Trp179fs (c.537del)?

CD96 p.Trp179fs (c.537del) is associated with C syndrome (ClinVar).

CD96 p.Trp179fs

c.537del · VCV3899989

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

C syndrome

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 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1

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

Variant & gene context

Gene: CD96
Protein: p.Trp179fs
Coding: c.537del
MANE Select: NM_005816
Type: Deletion
Location: chr3:111567640 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 179: a disulfide bond; the ig-like v-type 2 domain

Full CD96 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD96 p.Asp312fs Uncertain significance ★★ same condition
CD96 c.544-1477_544-1459del Uncertain significance ★ same condition
ZBED2 p.Arg179Gln Uncertain significance ★ ⚠ same residue
CD96 c.1249+1G>A Uncertain significance ★★ same condition
CD96 c.807+14A>C Benign/Likely benign ★★ same condition
CD96 c.1321+1G>A Likely pathogenic ★ same condition
CD96 c.807+2T>A Likely pathogenic ★ same condition
CD96 c.1181-12T>C Uncertain significance ★ 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/cd96-p-trp179fs (accessed [today's date]).

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