Is CD2 p.Arg243Gln (c.728G>A) pathogenic?

CD2 p.Arg243Gln (c.728G>A) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.0985); Ultra-rare (popmax 0.0167%, amr).

How common is CD2 p.Arg243Gln (c.728G>A) in the general population?

CD2 p.Arg243Gln (c.728G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about CD2 p.Arg243Gln (c.728G>A)?

AlphaMissense predicts likely benign (score 0.0985) — an in-silico prediction, not a clinical call.

CD2 p.Arg243Gln

c.728G>A · VCV3829432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0985 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0985	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -5.73	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 0.67	GERP -0.68, phastCons 0.086
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	19.97	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

Grpmax group 0.0167% Admixed American · 10/60,006 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00149% 24/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
African / African-American	0.00667%	14,992
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,052
European (non-Finnish)	0.000509%	196,625

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.Arg243Gln
Coding: c.728G>A
MANE Select: NM_001767
Type: single nucleotide variant
Location: chr1:116764598 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 243: the 'disordered' region

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

Similar variants

CD2 p.Arg243Leu 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.Arg263Gln Uncertain significance ★ ⚠ same type
CD2 p.Arg296Cys 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-arg243gln (accessed [today's date]).

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