Is COG2 p.Leu88= (c.264T>G) pathogenic?

COG2 p.Leu88= (c.264T>G) is classified Benign in COG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Leu88= (c.264T>G)?

COG2 p.Leu88= (c.264T>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.Leu88=

Q: How common is COG2 p.Leu88= (c.264T>G) in the general population?

COG2 p.Leu88= (c.264T>G) is common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.264T>G · rs16852160 · VCV672165

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.6%, afr) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -1.8
Overall
CADD	5.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.6% African / African-American · 7,739/73,046 alleles

Filtering AF 10.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.3%

Overall 0.674% 10,690/1,586,946 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.6%	9
Middle Eastern	0.916%	109
Remaining individualsnot grpmax-eligible	0.891%	112
Admixed American	0.711%	141
European (non-Finnish)	0.154%	649
East Asian	0.148%	677
South Asian	0.0876%	1,141
Finnishnot grpmax-eligible	0.0314%	3,189

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.Leu88=
Coding: c.264T>G
MANE Select: NM_007357
dbSNP: rs16852160
Type: single nucleotide variant
Location: chr1:230660787 (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-leu88 (accessed [today's date]).

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