Is CD2 p.Arg129Lys (c.386G>A) pathogenic?

CD2 p.Arg129Lys (c.386G>A) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-23). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00535%, afr).

How common is CD2 p.Arg129Lys (c.386G>A) in the general population?

CD2 p.Arg129Lys (c.386G>A) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about CD2 p.Arg129Lys (c.386G>A)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

CD2 p.Arg129Lys

c.386G>A · VCV4444721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.43	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -5.5	GERP -4.3
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	0.213	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 0.00535% African / African-American · 4/74,776 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000744% 12/1,612,090 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,694
European (non-Finnish)	0.000679%	147,344

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.Arg129Lys
Coding: c.386G>A
MANE Select: NM_001767
Type: single nucleotide variant
Location: chr1:116760405 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 129: an α-helix; the ig-like c2-type domain

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

Similar variants

CD2 p.Arg129Trp 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.Arg243Gln Uncertain significance ★ ⚠ same type
CD2 p.Arg243Leu 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-arg129lys (accessed [today's date]).

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