Is COG2 p.Asp338= (c.1014T>C) pathogenic?

COG2 p.Asp338= (c.1014T>C) is classified Benign/Likely benign in COG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). Rare (popmax 0.677%, nfe); Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Asp338= (c.1014T>C)?

COG2 p.Asp338= (c.1014T>C) is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How common is COG2 p.Asp338= (c.1014T>C) in the general population?

COG2 p.Asp338= (c.1014T>C) is rare (popmax 0.677%, nfe) (gnomAD).

How is COG2-CDG inherited?

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

COG2 p.Asp338=

c.1014T>C · rs113173809 · VCV478370

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.677%, nfe)

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 -1.4	GERP -1.1
Overall
CADD	3.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.677% European (non-Finnish) · 7,980/1,178,898 alleles

Filtering AF 0.664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.659%

Overall 0.571% 9,198/1,611,642 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.677%	148
Middle Eastern	0.528%	189
South Asian	0.506%	198
Remaining individualsnot grpmax-eligible	0.482%	207
Admixed American	0.325%	308
Finnishnot grpmax-eligible	0.15%	666
African / African-American	0.144%	694
Ashkenazi Jewishnot grpmax-eligible	0.0981%	1,019
East Asian	0.00223%	44,832

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.Asp338=
Coding: c.1014T>C
MANE Select: NM_007357
dbSNP: rs113173809
Type: single nucleotide variant
Location: chr1:230675112 (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.Asp338Asn Uncertain significance ★ ⚠ same residue
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

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-asp338 (accessed [today's date]).

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