Is COG7 p.Pro617= (c.1851C>T) pathogenic?

COG7 p.Pro617= (c.1851C>T) is classified Conflicting classifications of pathogenicity in COG7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0333%, amr); Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Pro617= (c.1851C>T)?

COG7 p.Pro617= (c.1851C>T) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How common is COG7 p.Pro617= (c.1851C>T) in the general population?

COG7 p.Pro617= (c.1851C>T) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

How is COG7-CDG inherited?

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

COG7 p.Pro617=

c.1851C>T · rs748835759 · VCV515731

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Conditions

COG7-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 -1.4	GERP -3.1
Overall
CADD	4.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Admixed American · 20/59,990 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00397% 64/1,613,978 alleles · ultra-rare exomes 56/1,461,864 · genomes 8/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0333%	2,999
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0112%	8,927
East Asian	0.00445%	22,447
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,446
European (non-Finnish)	0.00254%	39,334

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: COG7
Protein: p.Pro617=
Coding: c.1851C>T
MANE Select: NM_153603
dbSNP: rs748835759
Type: single nucleotide variant
Location: chr16:23398082 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.77

Full COG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG7-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG7-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG7 c.318+1G>A Likely pathogenic ★★ same condition
COG7 p.Ala606Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COG7 p.Arg444Ter Pathogenic/Likely pathogenic ★★ same condition
COG7 c.1475+4G>A Uncertain significance ★★ same condition
COG7 p.Ala194Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala222Thr Uncertain significance ★★ ⚠ same condition
COG7 p.Ala29Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala325Thr 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/cog7-p-pro617 (accessed [today's date]).

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