Is CD96 p.Asn464Asp (c.1390A>G) pathogenic?

CD96 p.Asn464Asp (c.1390A>G) is classified Uncertain significance in CD96 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-15). AlphaMissense: likely benign (0.0545); Absent from gnomAD v4.1; Associated with C syndrome.

What condition is associated with CD96 p.Asn464Asp (c.1390A>G)?

CD96 p.Asn464Asp (c.1390A>G) is associated with C syndrome (ClinVar).

How common is CD96 p.Asn464Asp (c.1390A>G) in the general population?

CD96 p.Asn464Asp (c.1390A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD96 p.Asn464Asp (c.1390A>G)?

AlphaMissense predicts likely benign (score 0.0545) — an in-silico prediction, not a clinical call.

CD96 p.Asn464Asp

c.1390A>G · rs1939421281 · VCV1028426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0545 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,244)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C syndrome

Computational evidence

Protein change
AlphaMissense	0.0545	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	7.308	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N480D vs ClinVar N464D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,244). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CD96
Protein: p.Asn464Asp
Coding: c.1390A>G
MANE Select: NM_005816
dbSNP: rs1939421281
Type: single nucleotide variant
Location: chr3:111638081 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 464: the 'disordered' region

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.Asp265Gly Uncertain significance ★ ⚠ same condition
CD96 p.Cys515Arg Uncertain significance ★ ⚠ same condition
CD96 p.Leu342Gln 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-asn464asp (accessed [today's date]).

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