Is COG2 p.Val61= (c.183C>T) pathogenic?

COG2 p.Val61= (c.183C>T) is classified Benign in COG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.38%, afr); Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Val61= (c.183C>T)?

COG2 p.Val61= (c.183C>T) is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How common is COG2 p.Val61= (c.183C>T) in the general population?

COG2 p.Val61= (c.183C>T) is low-frequency (popmax 1.38%, afr) (gnomAD).

How is COG2-CDG inherited?

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

COG2 p.Val61=

c.183C>T · rs79749108 · VCV709599

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, afr)

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 -5.6	GERP -4.4
Overall
CADD	1.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.38% African / African-American · 1,034/75,006 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0731% 1,180/1,613,948 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.38%	73
Remaining individualsnot grpmax-eligible	0.0976%	1,025
Admixed American	0.085%	1,177
Middle Eastern	0.066%	1,515
South Asian	0.00989%	10,115
European (non-Finnish)	0.00178%	56,188

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.Val61=
Coding: c.183C>T
MANE Select: NM_007357
dbSNP: rs79749108
Type: single nucleotide variant
Location: chr1:230659574 (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-val61 (accessed [today's date]).

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