Is COG7 p.Pro307= (c.921C>T) pathogenic?

COG7 p.Pro307= (c.921C>T) is classified Likely benign in COG7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0134%, eas); Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Pro307= (c.921C>T)?

COG7 p.Pro307= (c.921C>T) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How common is COG7 p.Pro307= (c.921C>T) in the general population?

COG7 p.Pro307= (c.921C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is COG7-CDG inherited?

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

COG7 p.Pro307=

c.921C>T · rs115610955 · VCV1673308

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -6.7	GERP -2.8
Overall
CADD	0.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.007% 113/1,614,212 alleles · ultra-rare exomes 101/1,461,870 · genomes 12/152,342 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.209%	478
Remaining individualsnot grpmax-eligible	0.0192%	5,209
East Asiangrpmax	0.0134%	7,480
European (non-Finnish)	0.00263%	38,066
South Asian	0.0022%	45,539

Ashkenazi Jewish 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: COG7
Protein: p.Pro307=
Coding: c.921C>T
MANE Select: NM_153603
dbSNP: rs115610955
Type: single nucleotide variant
Location: chr16:23424837 (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-pro307 (accessed [today's date]).

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