Is COG5 p.Glu575= (c.1725G>A) pathogenic?

COG5 p.Glu575= (c.1725G>A) is classified Conflicting classifications of pathogenicity in COG5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-16). Ultra-rare (popmax 0.0473%, nfe); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Glu575= (c.1725G>A)?

COG5 p.Glu575= (c.1725G>A) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Glu575= (c.1725G>A) in the general population?

COG5 p.Glu575= (c.1725G>A) is ultra-rare (popmax 0.0473%, nfe) (gnomAD).

How is COG5-CDG inherited?

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

COG5 p.Glu575=

c.1725G>A · rs145128460 · VCV511276

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, nfe)

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 -0.34	GERP -3.8, phastCons 0.006
Overall
CADD	6.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0473% European (non-Finnish) · 557/1,177,606 alleles

Filtering AF 0.044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0427%

Overall 0.0358% 577/1,610,486 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0473%	2,114
Remaining individualsnot grpmax-eligible	0.016%	6,231
African / African-American	0.00668%	14,961
Admixed American	0.00502%	19,934
Finnishnot grpmax-eligible	0.00313%	31,969

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.Glu575=
Coding: c.1725G>A
MANE Select: NM_006348
dbSNP: rs145128460
Type: single nucleotide variant
Location: chr7:107256756 (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 p.Glu575Val Uncertain significance ★ same residue
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

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-glu575 (accessed [today's date]).

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