Is CD209 p.Ala132Ser (c.394G>T) pathogenic?

CD209 p.Ala132Ser (c.394G>T) is classified Uncertain significance in CD209 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.1153); Very rare (popmax 0.000678%, nfe).

How common is CD209 p.Ala132Ser (c.394G>T) in the general population?

CD209 p.Ala132Ser (c.394G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CD209 p.Ala132Ser (c.394G>T)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

CD209 p.Ala132Ser

c.394G>T · rs769761518 · VCV2319238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.076	phastCons 0.002
Regional constraint	o/e 0.61	unconstrained · MANE · 437 bp · p 3.5e-06 · regional, not allelic
Overall
CADD	14.42	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 0.000678% European (non-Finnish) · 8/1,179,920 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,102 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.Ala132Ser
Coding: c.394G>T
MANE Select: NM_021155
dbSNP: rs769761518
Type: single nucleotide variant
Location: chr19:7745872 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 16 PDB
Residue 132: the '7 x approximate tandem repeats' region

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.Ala202Val Uncertain significance ★ ⚠ same type
CD209 p.Asp75Gly Uncertain significance ★ ⚠ same type
CD209 p.Cys284Ser 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-ala132ser (accessed [today's date]).

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