Is COG2 p.Asp687= (c.2061C>T) pathogenic?

COG2 p.Asp687= (c.2061C>T) is classified Likely benign in COG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0834%, sas); Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Asp687= (c.2061C>T)?

COG2 p.Asp687= (c.2061C>T) is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How common is COG2 p.Asp687= (c.2061C>T) in the general population?

COG2 p.Asp687= (c.2061C>T) is ultra-rare (popmax 0.0834%, sas) (gnomAD).

How is COG2-CDG inherited?

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

COG2 p.Asp687=

c.2061C>T · rs374676672 · VCV715155

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0834%, sas)

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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4
Overall
CADD	0.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0834% South Asian · 76/91,074 alleles

Filtering AF 0.0683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.0175% 282/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.32%	76
South Asiangrpmax	0.0834%	1,198
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.0147%	6,821
African / African-American	0.008%	12,504
East Asian	0.00446%	22,436
Admixed American	0.00167%	60,024

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: COG2
Protein: p.Asp687=
Coding: c.2061C>T
MANE Select: NM_007357
dbSNP: rs374676672
Type: single nucleotide variant
Location: chr1:230691510 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38
Residue 687: the 'disordered' region

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-asp687 (accessed [today's date]).

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