Is CD302 p.Pro7Arg (c.20C>G) pathogenic?

CD302 p.Pro7Arg (c.20C>G) is classified Uncertain significance in CD302 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.2243); Ultra-rare (popmax 0.0205%, mid).

How common is CD302 p.Pro7Arg (c.20C>G) in the general population?

CD302 p.Pro7Arg (c.20C>G) is ultra-rare (popmax 0.0205%, mid) (gnomAD).

What do computational predictors say about CD302 p.Pro7Arg (c.20C>G)?

AlphaMissense predicts likely benign (score 0.2243) — an in-silico prediction, not a clinical call.

CD302 p.Pro7Arg

c.20C>G · rs552282127 · VCV2322491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2243 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2243	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.24	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 2.2	GERP -0.18, phastCons 0.15
Regional constraint	o/e 1.05	unconstrained · MANE · 26 kb · p 0.38 · regional, not allelic
Overall
CADD	14.46	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 0.0205% Middle Eastern · 1/4,878 alleles

Filtering AF 0.00507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00365%

Overall 0.00108% 16/1,479,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0205%	4,878
South Asian	0.0102%	9,818
Remaining individualsnot grpmax-eligible	0.00349%	28,615
European (non-Finnish)	0.000446%	224,239

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: CD302
Protein: p.Pro7Arg
Coding: c.20C>G
MANE Select: NM_014880
dbSNP: rs552282127
Type: single nucleotide variant
Location: chr2:159798179 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.53 · 1 PDB

Full CD302 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD302 p.Ala5Thr Uncertain significance ★ ⚠ same type
CD302 p.Asp113Gly Uncertain significance ★ ⚠ same type
CD302 p.Leu6Arg Uncertain significance ★ ⚠ same type
CD302 p.Leu9Arg Uncertain significance ★ ⚠ same type
CD302 p.Pro12Ser Uncertain significance ★ ⚠ same type
LY75-CD302 p.Ser1840Pro 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/cd302-p-pro7arg (accessed [today's date]).

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