Is CD96 p.Pro162Ser (c.484C>T) pathogenic?

CD96 p.Pro162Ser (c.484C>T) is classified Conflicting classifications of pathogenicity in CD96 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-14). AlphaMissense: likely benign (0.2851); Very rare (popmax 8.51e-05%, nfe); Associated with C syndrome.

What condition is associated with CD96 p.Pro162Ser (c.484C>T)?

CD96 p.Pro162Ser (c.484C>T) is associated with C syndrome (ClinVar).

How common is CD96 p.Pro162Ser (c.484C>T) in the general population?

CD96 p.Pro162Ser (c.484C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about CD96 p.Pro162Ser (c.484C>T)?

AlphaMissense predicts likely benign (score 0.2851) — an in-silico prediction, not a clinical call.

CD96 p.Pro162Ser

c.484C>T · rs371659001 · VCV2298818

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C syndrome

Computational evidence

Protein change
AlphaMissense	0.2851	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -6.73	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 3.1	GERP 2.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 108 kb · p 0.013 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,156 alleles

Overall 6.87e-05% 1/1,456,438 alleles · very rare

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.Pro162Ser
Coding: c.484C>T
MANE Select: NM_005816
dbSNP: rs371659001
Type: single nucleotide variant
Location: chr3:111567588 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 162: the ig-like v-type 2 domain

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.Arg162Lys 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-pro162ser (accessed [today's date]).

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