Is CD96 p.Thr322= (c.966A>G) pathogenic?

CD96 p.Thr322= (c.966A>G) is classified Benign in CD96 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Common (popmax 8.22%, amr) — too common for a highly-penetrant pathogenic allele.

CD96 p.Thr322=

Q: How common is CD96 p.Thr322= (c.966A>G) in the general population?

CD96 p.Thr322= (c.966A>G) is common (popmax 8.22%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.966A>G · rs145863419 · VCV1559716

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.22%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.96, phastCons 0.15
Overall
CADD	3.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.22% Admixed American · 4,931/60,020 alleles

Filtering AF 8.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.95%

Overall 0.327% 5,278/1,613,412 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	8.22%	12
Remaining individualsnot grpmax-eligible	0.306%	327
African / African-American	0.108%	927
East Asian	0.0602%	1,661
European (non-Finnish)	0.00407%	24,570

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: CD96
Protein: p.Thr322=
Coding: c.966A>G
MANE Select: NM_005816
dbSNP: rs145863419
Type: single nucleotide variant
Location: chr3:111600793 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 322: a disulfide bond; the ig-like c2-type domain

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

Similar variants

CD96 c.1249+1G>A Uncertain significance ★★ same type
CD96 c.544-1512C>T Uncertain significance ★★ ⚠ same type
CD96 p.Asp205Gly Uncertain significance ★★ ⚠ same type
CD96 p.Asp224Asn Uncertain significance ★★ ⚠ same type
CD96 p.Ile151Thr Uncertain significance ★★ ⚠ same type
CD96 p.Leu120Pro Uncertain significance ★★ ⚠ same type
CD96 p.Lys500Arg Uncertain significance ★★ ⚠ same type
CD96 p.Pro346Ser 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/cd96-p-thr322 (accessed [today's date]).

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