Is CD207 p.Val278Ala (c.833T>C) pathogenic?

CD207 p.Val278Ala (c.833T>C) is classified Benign in CD207 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). AlphaMissense: likely benign (0.053); Common (popmax 68.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CD207-related disorder.

What condition is associated with CD207 p.Val278Ala (c.833T>C)?

CD207 p.Val278Ala (c.833T>C) is associated with CD207-related disorder (ClinVar).

What do computational predictors say about CD207 p.Val278Ala (c.833T>C)?

AlphaMissense predicts likely benign (score 0.053) — an in-silico prediction, not a clinical call.

CD207 p.Val278Ala

Q: How common is CD207 p.Val278Ala (c.833T>C) in the general population?

CD207 p.Val278Ala (c.833T>C) is common (popmax 68.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.833T>C · rs741326 · VCV3059640

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.053 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 68.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD207-related disorder

Computational evidence

Protein change
AlphaMissense	0.053	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -4.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7
Regional constraint	o/e 0.98	unconstrained · MANE · 4,723 bp · p 0.62 · regional, not allelic
Overall
CADD	0.004	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 68.7% East Asian · 30,722/44,746 alleles

Filtering AF 68% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.8%

Overall 44.7% 714,444/1,598,148 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	68.7%	1
South Asian	55.4%	2
Finnishnot grpmax-eligible	53.4%	2
African / African-American	47.6%	2
Admixed American	47%	2
Remaining individualsnot grpmax-eligible	44.4%	2
Middle Eastern	43.6%	2
European (non-Finnish)	42.5%	2
Amishnot grpmax-eligible	41.4%	2
Ashkenazi Jewishnot grpmax-eligible	33.8%	3

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.Val278Ala
Coding: c.833T>C
MANE Select: NM_015717
dbSNP: rs741326
Type: single nucleotide variant
Location: chr2:70831704 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.13 · 22 PDB
Residue 278: a UniProt-annotated variant site (no effect on mannose-binding ability); an α-helix; the c-type lectin domain; a disulfide bond

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

Disease context

CD207-related disorder

Similar variants

CD207 p.Ala55Val Benign same condition
CD207 p.Ala61= Likely benign same condition
CD207 p.Gln136Glu Benign same condition
CD207 p.Glu114Val Benign same condition
CD207 p.Pro328= Benign same condition
CD207 p.Ser237= Benign same condition
CD207 p.Thr314= Benign same condition
CD207 p.Val78= Benign same condition

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-val278ala (accessed [today's date]).

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