Is COG2 c.2115+18G>A pathogenic?

COG2 c.2115+18G>A is classified Likely benign in COG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-13). Ultra-rare (popmax 0.0998%, mid); Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 c.2115+18G>A?

COG2 c.2115+18G>A is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How common is COG2 c.2115+18G>A in the general population?

COG2 c.2115+18G>A is ultra-rare (popmax 0.0998%, mid) (gnomAD).

How is COG2-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COG2 c.2115+18G>A

rs199661448 · VCV2064675

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0998%, mid)

Conditions

congenital disorder of glycosylation, type IIq

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -3.3
Non-coding constraint	Z 3.54	1 kb window · o/e 0.77 · regional · uncalibrated
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0998% Middle Eastern · 5/5,012 alleles

Filtering AF 0.0393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0255%

Overall 0.0102% 163/1,597,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0998%	1,002
South Asian	0.0348%	2,874
European (non-Finnish)	0.0102%	9,842
Remaining individualsnot grpmax-eligible	0.00973%	10,277
East Asian	0.00224%	44,574
Admixed American	0.00174%	57,622

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: COG2
Coding: c.2115+18G>A
MANE Select: NM_007357
dbSNP: rs199661448
Type: single nucleotide variant
Location: chr1:230691582 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38

Full COG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation, type IIq — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

COG2 p.Ala160Val Uncertain significance ★★ ⚠ same condition
COG2 p.Ala339Pro Uncertain significance ★★ ⚠ same condition
COG2 p.Arg138Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg241Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg356Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg356Trp Uncertain significance ★★ ⚠ same condition
COG2 p.Arg39Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg39Trp Uncertain significance ★★ ⚠ 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/cog2-c-2115-plus-18g-a (accessed [today's date]).

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