Is COG1 p.Pro174= (c.522T>C) pathogenic?

COG1 p.Pro174= (c.522T>C) is classified Benign/Likely benign in COG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Low-frequency (popmax 3.32%, eas); Associated with COG1-congenital disorder of glycosylation.

What condition is associated with COG1 p.Pro174= (c.522T>C)?

COG1 p.Pro174= (c.522T>C) is associated with COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Pro174= (c.522T>C) in the general population?

COG1 p.Pro174= (c.522T>C) is low-frequency (popmax 3.32%, eas) (gnomAD).

How is COG1-CDG inherited?

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

COG1 p.Pro174=

c.522T>C · rs75460067 · VCV324961

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.32%, eas)

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 -4.6	GERP -3.5
Overall
CADD	2.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.32% East Asian · 1,488/44,882 alleles

Filtering AF 3.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.347% 5,609/1,614,118 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.26%	23
East Asiangrpmax	3.32%	30
South Asian	0.627%	160
Remaining individualsnot grpmax-eligible	0.422%	237
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0459%	2,177
African / African-American	0.016%	6,255
Admixed American	0.00167%	60,016

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro174=
Coding: c.522T>C
MANE Select: NM_018714
dbSNP: rs75460067
Type: single nucleotide variant
Location: chr17:73196713 (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-pro174 (accessed [today's date]).

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