Is CD96 p.Lys4Asn (c.12A>T) pathogenic?

CD96 p.Lys4Asn (c.12A>T) is classified Uncertain significance in CD96 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1998); Absent from gnomAD v4.1; Associated with C syndrome.

What condition is associated with CD96 p.Lys4Asn (c.12A>T)?

CD96 p.Lys4Asn (c.12A>T) is associated with C syndrome (ClinVar).

How common is CD96 p.Lys4Asn (c.12A>T) in the general population?

CD96 p.Lys4Asn (c.12A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD96 p.Lys4Asn (c.12A>T)?

AlphaMissense predicts likely benign (score 0.1998) — an in-silico prediction, not a clinical call.

CD96 p.Lys4Asn

c.12A>T · VCV3362818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C syndrome

Computational evidence

Protein change
AlphaMissense	0.1998	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -6.34	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 2.1	GERP -0.013, phastCons 0.99
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	21.6	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD96
Protein: p.Lys4Asn
Coding: c.12A>T
MANE Select: NM_005816
Type: single nucleotide variant
Location: chr3:111542260 (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

ZBED2 p.Arg4Gln 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
CD96 p.Asn464Asp Uncertain significance ★ ⚠ same condition
CD96 p.Asp265Gly 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-lys4asn (accessed [today's date]).

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