Is CD2 p.Ile94Met (c.282T>G) pathogenic?

CD2 p.Ile94Met (c.282T>G) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: ambiguous (0.3708); Ultra-rare (popmax 0.0165%, sas).

How common is CD2 p.Ile94Met (c.282T>G) in the general population?

CD2 p.Ile94Met (c.282T>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about CD2 p.Ile94Met (c.282T>G)?

AlphaMissense predicts ambiguous (score 0.3708) — an in-silico prediction, not a clinical call.

CD2 p.Ile94Met

c.282T>G · rs779858103 · VCV2238530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Computational evidence

Protein change
AlphaMissense	0.3708	ambiguous
REVEL	0.37	indeterminate
SaProt	LLR -10.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -2.7, phastCons 0.04
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	14.83	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 0.0165% South Asian · 15/91,030 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00112% 18/1,612,690 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,069
Remaining individualsnot grpmax-eligible	0.0048%	20,818

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.Ile94Met
Coding: c.282T>G
MANE Select: NM_001767
dbSNP: rs779858103
Type: single nucleotide variant
Location: chr1:116754851 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 94: a β-strand; the ig-like v-type domain

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

Similar variants

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
CD2 p.Arg263Gln 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-ile94met (accessed [today's date]).

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