Is DCC c.91+7G>A pathogenic?

DCC c.91+7G>A is classified Benign in DCC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-21). Common (popmax 6.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with esophageal cancer.

What condition is associated with DCC c.91+7G>A?

DCC c.91+7G>A is associated with esophageal cancer, colorectal cancer, gaze palsy, familial horizontal, with progressive scoliosis, 2 (ClinVar).

DCC c.91+7G>A

Q: How common is DCC c.91+7G>A in the general population?

DCC c.91+7G>A is common (popmax 6.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs112558388 · VCV709096

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

esophageal cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -1.3, phastCons 1
Non-coding constraint	Z -2.67	1 kb window · o/e 1.18 · regional · uncalibrated
Overall
CADD	13.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.7% African / African-American · 5,004/74,738 alleles

Filtering AF 6.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.48%

Overall 0.351% 5,637/1,605,918 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.7%	15
Remaining individualsnot grpmax-eligible	0.472%	212
Admixed American	0.4%	250
Middle Eastern	0.165%	605
South Asian	0.0297%	3,367
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,781
European (non-Finnish)	0.00512%	19,544

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: DCC
Coding: c.91+7G>A
MANE Select: NM_005215
dbSNP: rs112558388
Type: single nucleotide variant
Location: chr18:52340885 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB

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

Disease context

esophageal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer gaze palsy, familial horizontal, with progressive scoliosis, 2

Similar variants

DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Arg275Ter Pathogenic ★★ same condition
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Gly803Arg Uncertain significance ★★ ⚠ same condition
DCC c.2053+13A>G Benign ★★ same condition
DCC c.2053+9T>C Benign/Likely benign ★★ same condition
DCC c.3130+10A>G Benign ★★ same condition
DCC p.Arg201Gly 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/dcc-c-91-plus-7g-a (accessed [today's date]).

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