Is COG5 p.Ile747= (c.2241C>T) pathogenic?

COG5 p.Ile747= (c.2241C>T) is classified Likely benign in COG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Very rare (popmax 0.0022%, sas); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Ile747= (c.2241C>T)?

COG5 p.Ile747= (c.2241C>T) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Ile747= (c.2241C>T) in the general population?

COG5 p.Ile747= (c.2241C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is COG5-CDG inherited?

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

COG5 p.Ile747=

c.2241C>T · rs753572639 · VCV2783421

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

COG5-congenital disorder of glycosylation

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 0.9	GERP -0.79, phastCons 0.021
Overall
CADD	7.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.000254%	393,301

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: COG5
Protein: p.Ile747=
Coding: c.2241C>T
MANE Select: NM_006348
dbSNP: rs753572639
Type: single nucleotide variant
Location: chr7:107211153 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37

Full COG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG5-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG5-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

COG5 c.1475+1G>A Likely pathogenic ★★ same condition
COG5 c.2295+2T>C Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg205Ter Pathogenic ★★ same condition
COG5 p.Arg283Ter Pathogenic ★★ same condition
COG5 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg690Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg708Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ 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/cog5-p-ile747 (accessed [today's date]).

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