Is CD209 p.Glu353Lys (c.1057G>A) pathogenic?

CD209 p.Glu353Lys (c.1057G>A) is classified Uncertain significance in CD209 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.099); Very rare (popmax 0.00167%, amr).

How common is CD209 p.Glu353Lys (c.1057G>A) in the general population?

CD209 p.Glu353Lys (c.1057G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD209 p.Glu353Lys (c.1057G>A)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

CD209 p.Glu353Lys

c.1057G>A · rs1568509808 · VCV2269724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -2
Regional constraint	o/e 0.99	unconstrained · MANE · 2,490 bp · p 0.88 · regional, not allelic
Overall
CADD	16.28	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 0.00167% Admixed American · 1/59,996 alleles

Overall 0.000657% 1/152,150 alleles · very rare

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.Glu353Lys
Coding: c.1057G>A
MANE Select: NM_021155
dbSNP: rs1568509808
Type: single nucleotide variant
Location: chr19:7743197 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 16 PDB
Residue 353: the c-type lectin domain; a disulfide bond

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

Similar variants

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
CD209 p.Asp75Gly 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-glu353lys (accessed [today's date]).

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