Is CD209 p.Lys379Glu (c.1135A>G) pathogenic?

CD209 p.Lys379Glu (c.1135A>G) is classified Uncertain significance in CD209 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: ambiguous (0.4561); Very rare (popmax 8.47e-05%, nfe).

How common is CD209 p.Lys379Glu (c.1135A>G) in the general population?

CD209 p.Lys379Glu (c.1135A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD209 p.Lys379Glu (c.1135A>G)?

AlphaMissense predicts ambiguous (score 0.4561) — an in-silico prediction, not a clinical call.

CD209 p.Lys379Glu

c.1135A>G · rs1196424523 · VCV2242579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4561	ambiguous
REVEL	0.043	moderately benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -0.54
Regional constraint	o/e 0.99	unconstrained · MANE · 2,490 bp · p 0.88 · regional, not allelic
Overall
CADD	18.2	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 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,890 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.Lys379Glu
Coding: c.1135A>G
MANE Select: NM_021155
dbSNP: rs1196424523
Type: single nucleotide variant
Location: chr19:7743119 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 16 PDB
Residue 379: a β-strand

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-lys379glu (accessed [today's date]).

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