Is CD96 p.Gly363Val (c.1088G>T) pathogenic?

CD96 p.Gly363Val (c.1088G>T) is classified Uncertain significance in CD96 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: likely benign (0.1625); Very rare (popmax 0.00502%, amr).

How common is CD96 p.Gly363Val (c.1088G>T) in the general population?

CD96 p.Gly363Val (c.1088G>T) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about CD96 p.Gly363Val (c.1088G>T)?

AlphaMissense predicts likely benign (score 0.1625) — an in-silico prediction, not a clinical call.

CD96 p.Gly363Val

c.1088G>T · rs1283203445 · VCV2306978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1625	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.47	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.64	loss · gain 0.60 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.5	GERP 0.5, phastCons 0.88
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	20.1	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 G379V vs ClinVar G363V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00502% Admixed American · 3/59,794 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000596% 8/1,341,774 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,931
European (non-Finnish)	0.000467%	214,150

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.Gly363Val
Coding: c.1088G>T
MANE Select: NM_005816
dbSNP: rs1283203445
Type: single nucleotide variant
Location: chr3:111606700 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 363: 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-gly363val (accessed [today's date]).

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