Is CD209 p.Cys284Ser (c.851G>C) pathogenic?

CD209 p.Cys284Ser (c.851G>C) is classified Uncertain significance in CD209 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.9899); Absent from gnomAD v4.1.

How common is CD209 p.Cys284Ser (c.851G>C) in the general population?

CD209 p.Cys284Ser (c.851G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD209 p.Cys284Ser (c.851G>C)?

AlphaMissense predicts likely pathogenic (score 0.9899) — an in-silico prediction, not a clinical call.

CD209 p.Cys284Ser

c.851G>C · VCV4650513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9899 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9899	likely pathogenic · top 1% in CD209
REVEL	0.663	pathogenic-leaning
SaProt	LLR -12.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 0.97
Regional constraint	o/e 0.99	unconstrained · MANE · 2,490 bp · p 0.88 · regional, not allelic
Overall
CADD	19.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD209
Protein: p.Cys284Ser
Coding: c.851G>C
MANE Select: NM_021155
Type: single nucleotide variant
Location: chr19:7744990 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 16 PDB
Residue 284: the c-type lectin domain; a disulfide bond; an α-helix

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-cys284ser (accessed [today's date]).

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