Is CD96 p.Thr264Met (c.791C>T) pathogenic?

CD96 p.Thr264Met (c.791C>T) is classified Pathogenic in CD96 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-10-01). AlphaMissense: likely benign (0.0748); Ultra-rare (popmax 0.0558%, eas); Associated with C syndrome.

What condition is associated with CD96 p.Thr264Met (c.791C>T)?

CD96 p.Thr264Met (c.791C>T) is associated with C syndrome (ClinVar).

How common is CD96 p.Thr264Met (c.791C>T) in the general population?

CD96 p.Thr264Met (c.791C>T) is ultra-rare (popmax 0.0558%, eas) (gnomAD).

What do computational predictors say about CD96 p.Thr264Met (c.791C>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

CD96 p.Thr264Met

c.791C>T · rs119477056 · VCV4640

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0558%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C syndrome

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign ⚠ discordant with ClinVar
REVEL	0.271	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor loss, 39 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -2.2	GERP -3.1
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	0.099	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T280M vs ClinVar T264M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0558% East Asian · 25/44,814 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.00261% 42/1,607,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0558%	1,793
South Asian	0.0022%	45,473
Remaining individualsnot grpmax-eligible	0.00161%	62,284
European (non-Finnish)	0.00119%	83,898

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.Thr264Met
Coding: c.791C>T
MANE Select: NM_005816
dbSNP: rs119477056
Type: single nucleotide variant
Location: chr3:111585362 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB

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 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
CD96 p.Asn464Asp Uncertain significance ★ ⚠ same condition
CD96 p.Asp265Gly Uncertain significance ★ ⚠ same condition
CD96 p.Cys515Arg 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-thr264met (accessed [today's date]).

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