Is CD2 p.Arg296Cys (c.886C>T) pathogenic?

CD2 p.Arg296Cys (c.886C>T) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.2207); Rare (popmax 0.231%, mid).

How common is CD2 p.Arg296Cys (c.886C>T) in the general population?

CD2 p.Arg296Cys (c.886C>T) is rare (popmax 0.231%, mid) (gnomAD).

What do computational predictors say about CD2 p.Arg296Cys (c.886C>T)?

AlphaMissense predicts likely benign (score 0.2207) — an in-silico prediction, not a clinical call.

CD2 p.Arg296Cys

c.886C>T · rs377222693 · VCV2368965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2207 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.231%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2207	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 1.2, phastCons 0.95
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	22.2	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 0.231% Middle Eastern · 14/6,062 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.0096% 155/1,614,092 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.231%	433
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.0167%	6,002
South Asian	0.00988%	10,120
European (non-Finnish)	0.0089%	11,238
African / African-American	0.00533%	18,751

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: CD2
Protein: p.Arg296Cys
Coding: c.886C>T
MANE Select: NM_001767
dbSNP: rs377222693
Type: single nucleotide variant
Location: chr1:116768613 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 296: the 'disordered' region

Full CD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2 p.Arg296His Uncertain significance ★ ⚠ same residue
CD2 p.Ala270Thr Uncertain significance ★ ⚠ same type
CD2 p.Ala292Ser Uncertain significance ★ ⚠ same type
CD2 p.Ala342Thr Uncertain significance ★ ⚠ same type
CD2 p.Arg129Lys Uncertain significance ★ ⚠ same type
CD2 p.Arg129Trp Uncertain significance ★ ⚠ same type
CD2 p.Arg243Gln Uncertain significance ★ ⚠ same type
CD2 p.Arg243Leu 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/cd2-p-arg296cys (accessed [today's date]).

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