Is CD96 p.Ala283Gly (c.848C>G) pathogenic?

CD96 p.Ala283Gly (c.848C>G) is classified Uncertain significance in CD96 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.213); Absent from gnomAD v4.1; Associated with CD96-related disorder.

What condition is associated with CD96 p.Ala283Gly (c.848C>G)?

CD96 p.Ala283Gly (c.848C>G) is associated with CD96-related disorder (ClinVar).

How common is CD96 p.Ala283Gly (c.848C>G) in the general population?

CD96 p.Ala283Gly (c.848C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD96 p.Ala283Gly (c.848C>G)?

AlphaMissense predicts likely benign (score 0.213) — an in-silico prediction, not a clinical call.

CD96 p.Ala283Gly

c.848C>G · rs1937342582 · VCV3054074

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.213 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD96-related disorder

Computational evidence

Protein change
AlphaMissense	0.213	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.33	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	27.9	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 A299G vs ClinVar A283G) — verify the residue.

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.Ala283Gly
Coding: c.848C>G
MANE Select: NM_005816
dbSNP: rs1937342582
Type: single nucleotide variant
Location: chr3:111598160 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 283: the ig-like c2-type domain

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

Disease context

CD96-related disorder

Similar variants

CD96 c.1180+38A>T Likely benign same condition
CD96 c.*5G>A Likely benign same condition
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

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-ala283gly (accessed [today's date]).

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