Is CD209 p.Arg221Gln (c.662G>A) pathogenic?

CD209 p.Arg221Gln (c.662G>A) is classified Benign in CD209 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-31). AlphaMissense: likely benign (0.0657); Low-frequency (popmax 4%, afr); Associated with CD209-related disorder.

What condition is associated with CD209 p.Arg221Gln (c.662G>A)?

CD209 p.Arg221Gln (c.662G>A) is associated with CD209-related disorder (ClinVar).

How common is CD209 p.Arg221Gln (c.662G>A) in the general population?

CD209 p.Arg221Gln (c.662G>A) is low-frequency (popmax 4%, afr) (gnomAD).

What do computational predictors say about CD209 p.Arg221Gln (c.662G>A)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

CD209 p.Arg221Gln

c.662G>A · rs41335247 · VCV3038490

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD209-related disorder

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.13	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 -4.2
Regional constraint	o/e 0.61	unconstrained · MANE · 437 bp · p 3.5e-06 · regional, not allelic
Overall
CADD	0.081	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 4% African / African-American · 1,781/44,540 alleles

Filtering AF 3.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.78%

Overall 0.318% 1,962/617,018 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4%	25
Admixed American	0.245%	408
Remaining individualsnot grpmax-eligible	0.216%	464
Middle Eastern	0.0876%	1,142
South Asian	0.00981%	10,198
European (non-Finnish)	0.00817%	12,237
East Asian	0.00274%	36,482

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: CD209
Protein: p.Arg221Gln
Coding: c.662G>A
MANE Select: NM_021155
dbSNP: rs41335247
Type: single nucleotide variant
Location: chr19:7745604 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 16 PDB
Residue 221: the '7 x approximate tandem repeats' region

Full CD209 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD209-related disorder

Similar variants

CD209 p.Arg309= Benign same condition
CD209 p.Gln189Leu Uncertain significance ★★ ⚠ same type
CD209 p.Glu214Asp Uncertain significance ★★ ⚠ same type
CD209 p.Ala357= Benign ★★ same type
CD209 p.Ala395= Benign ★★ same type
CD209 p.Asp331= Benign ★★ same type
CD209 p.Ala132Ser Uncertain significance ★ ⚠ same type
CD209 p.Ala202Val 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/cd209-p-arg221gln (accessed [today's date]).

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