Is CD207 p.Ala246Val (c.737C>T) pathogenic?

CD207 p.Ala246Val (c.737C>T) is classified Uncertain significance in CD207 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.1479); Ultra-rare (popmax 0.033%, mid).

How common is CD207 p.Ala246Val (c.737C>T) in the general population?

CD207 p.Ala246Val (c.737C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CD207 p.Ala246Val (c.737C>T)?

AlphaMissense predicts likely benign (score 0.1479) — an in-silico prediction, not a clinical call.

CD207 p.Ala246Val

c.737C>T · rs527591997 · VCV2372832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1479 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1479	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.52	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 3.1	phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 4,723 bp · p 0.62 · regional, not allelic
Overall
CADD	18.23	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.033% Middle Eastern · 2/6,052 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00578% 93/1,610,364 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,026
African / African-American	0.024%	4,162
Remaining individualsnot grpmax-eligible	0.00962%	10,393
European (non-Finnish)	0.00527%	18,979
Admixed American	0.005%	20,002
South Asian	0.0022%	45,492

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.Ala246Val
Coding: c.737C>T
MANE Select: NM_015717
dbSNP: rs527591997
Type: single nucleotide variant
Location: chr2:70831800 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.13 · 22 PDB
Residue 246: 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

Similar variants

CD207 p.Ala246Glu Uncertain significance ★ ⚠ same residue
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.Ala55Thr Uncertain significance ★ ⚠ same type
CD207 p.Ala7Ser Uncertain significance ★ ⚠ same type
CD207 p.Arg120Cys 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-ala246val (accessed [today's date]).

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