Is COG1 p.Ser491= (c.1473C>T) pathogenic?

COG1 p.Ser491= (c.1473C>T) is classified Benign in COG1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 19.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with COG1-congenital disorder of glycosylation.

What condition is associated with COG1 p.Ser491= (c.1473C>T)?

COG1 p.Ser491= (c.1473C>T) is associated with COG1-congenital disorder of glycosylation (ClinVar).

How is COG1-CDG inherited?

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

COG1 p.Ser491=

Q: How common is COG1 p.Ser491= (c.1473C>T) in the general population?

COG1 p.Ser491= (c.1473C>T) is common (popmax 19.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1473C>T · rs1551036 · VCV95913

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 19.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

COG1-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 -10	GERP -3.2
Overall
CADD	1.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.8% South Asian · 17,999/91,082 alleles

Filtering AF 19.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.4%

Overall 17.7% 285,270/1,614,120 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	19.8%	5
European (non-Finnish)	19%	5
Amishnot grpmax-eligible	18.8%	5
Remaining individualsnot grpmax-eligible	17.4%	6
Middle Eastern	17.1%	6
Ashkenazi Jewishnot grpmax-eligible	15.6%	6
Finnishnot grpmax-eligible	14.9%	7
East Asian	14.5%	7
Admixed American	13.2%	8
African / African-American	3.06%	33

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: COG1
Protein: p.Ser491=
Coding: c.1473C>T
MANE Select: NM_018714
dbSNP: rs1551036
Type: single nucleotide variant
Location: chr17:73201300 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.82

Full COG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG1 c.1070+5G>A Pathogenic ★★ same condition
COG1 p.Arg336Ter Pathogenic ★★ same condition
COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same condition
COG1 p.Ala143Thr Uncertain significance ★★ same condition
COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala385Thr 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/cog1-p-ser491 (accessed [today's date]).

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