Is CD207 p.Trp264Arg (c.790T>C) pathogenic?

CD207 p.Trp264Arg (c.790T>C) is classified Uncertain significance in CD207 (ClinVar, Single submitter, 3 submitters; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.9558); Rare (popmax 0.419%, nfe); Associated with Birbeck granule deficiency.

What condition is associated with CD207 p.Trp264Arg (c.790T>C)?

CD207 p.Trp264Arg (c.790T>C) is associated with Birbeck granule deficiency (ClinVar).

How common is CD207 p.Trp264Arg (c.790T>C) in the general population?

CD207 p.Trp264Arg (c.790T>C) is rare (popmax 0.419%, nfe) (gnomAD).

What do computational predictors say about CD207 p.Trp264Arg (c.790T>C)?

AlphaMissense predicts likely pathogenic (score 0.9558) — an in-silico prediction, not a clinical call.

CD207 p.Trp264Arg

c.790T>C · rs200837270 · VCV5337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9558 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.419%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Birbeck granule deficiency

Computational evidence

Protein change
AlphaMissense	0.9558	likely pathogenic · top 2% in CD207
REVEL	0.405	indeterminate
SaProt	LLR -13.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 4,723 bp · p 0.62 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.419% European (non-Finnish) · 4,947/1,179,636 alleles

Filtering AF 0.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.406%

Overall 0.335% 5,401/1,613,744 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.419%	238
Ashkenazi Jewishnot grpmax-eligible	0.257%	390
Remaining individualsnot grpmax-eligible	0.229%	437
Admixed American	0.107%	938
South Asian	0.0867%	1,153
African / African-American	0.068%	1,471
Finnishnot grpmax-eligible	0.0625%	1,600
Middle Eastern	0.0165%	6,062

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: CD207
Protein: p.Trp264Arg
Coding: c.790T>C
MANE Select: NM_015717
dbSNP: rs200837270
Type: single nucleotide variant
Location: chr2:70831747 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.13 · 22 PDB
Residue 264: a UniProt-annotated variant site (in birgd; abolishes mannose-binding ability); a β-strand; the c-type lectin domain; a disulfide bond

Full CD207 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Birbeck granule deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD207 p.Asn134= Uncertain significance ★ same condition
CD207 p.Arg66Gln Benign ★★ same type
CD207 p.Ala10Val Uncertain significance ★ ⚠ same type
CD207 p.Ala135Thr Uncertain significance ★ ⚠ same type
CD207 p.Ala152Val Uncertain significance ★ ⚠ same type
CD207 p.Ala246Glu Uncertain significance ★ ⚠ same type
CD207 p.Ala246Val Uncertain significance ★ ⚠ same type
CD207 p.Ala55Thr 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/cd207-p-trp264arg (accessed [today's date]).

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