Is CD207 p.Gln136Glu (c.406C>G) pathogenic?

CD207 p.Gln136Glu (c.406C>G) is classified Benign in CD207 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). AlphaMissense: likely benign (0.0685); Common (popmax 32.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with CD207-related disorder.

What condition is associated with CD207 p.Gln136Glu (c.406C>G)?

CD207 p.Gln136Glu (c.406C>G) is associated with CD207-related disorder (ClinVar).

What do computational predictors say about CD207 p.Gln136Glu (c.406C>G)?

AlphaMissense predicts likely benign (score 0.0685) — an in-silico prediction, not a clinical call.

CD207 p.Gln136Glu

Q: How common is CD207 p.Gln136Glu (c.406C>G) in the general population?

CD207 p.Gln136Glu (c.406C>G) is common (popmax 32.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.406C>G · rs17718987 · VCV3060755

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0685 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 32.1%, nfe) — 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	0.0685	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.44	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 0.55	GERP -1.4
Regional constraint	o/e 0.98	unconstrained · MANE · 4,723 bp · p 0.62 · regional, not allelic
Overall
CADD	10.24	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 32.1% European (non-Finnish) · 378,555/1,179,670 alleles

Filtering AF 32% ClinGen BA1/BS1 input FAF95, joint · FAF99 32%

Overall 28.2% 455,693/1,613,668 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	44.9%	2
European (non-Finnish)grpmax	32.1%	3
Ashkenazi Jewishnot grpmax-eligible	31.3%	3
Middle Eastern	29.8%	3
Remaining individualsnot grpmax-eligible	26.6%	4
Finnishnot grpmax-eligible	25%	4
South Asian	20.8%	5
Admixed American	15.2%	7
African / African-American	6.61%	15
East Asian	0.12%	831

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln136Glu
Coding: c.406C>G
MANE Select: NM_015717
dbSNP: rs17718987
Type: single nucleotide variant
Location: chr2:70833805 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.13 · 22 PDB
Residue 136: a UniProt-annotated variant site (in)

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.Glu114Val Benign same condition
CD207 p.Pro328= Benign same condition
CD207 p.Ser237= Benign same condition
CD207 p.Thr314= Benign same condition
CD207 p.Val278Ala 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-gln136glu (accessed [today's date]).

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