Is COG2 p.Ter739= (c.2217A>G) pathogenic?

COG2 p.Ter739= (c.2217A>G) is classified Benign in COG2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 55.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Ter739= (c.2217A>G)?

COG2 p.Ter739= (c.2217A>G) is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How is COG2-CDG inherited?

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

COG2 p.Ter739=

Q: How common is COG2 p.Ter739= (c.2217A>G) in the general population?

COG2 p.Ter739= (c.2217A>G) is common (popmax 55.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2217A>G · rs1051038 · VCV1164695

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Common

common (popmax 55.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

congenital disorder of glycosylation, type IIq

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.1, phastCons 0.94
Overall
CADD	5.904	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.9% East Asian · 24,938/44,628 alleles

Filtering AF 55.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.1%

Overall 23.6% 377,161/1,595,614 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	55.9%	2
Admixed American	48.2%	2
Amishnot grpmax-eligible	35.8%	3
South Asian	29%	3
Finnishnot grpmax-eligible	27.8%	4
Remaining individualsnot grpmax-eligible	24.5%	4
African / African-American	21.3%	5
European (non-Finnish)	20.8%	5
Ashkenazi Jewishnot grpmax-eligible	17.9%	6
Middle Eastern	17.4%	6

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
Protein: p.Ter739=
Coding: c.2217A>G
MANE Select: NM_007357
dbSNP: rs1051038
Type: single nucleotide variant
Location: chr1:230693393 (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-p-ter739 (accessed [today's date]).

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