Is COG5 p.Val80fs (c.237del) pathogenic?

COG5 p.Val80fs (c.237del) is classified Pathogenic in COG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-07). Very rare (popmax 0.00668%, eas); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Val80fs (c.237del)?

COG5 p.Val80fs (c.237del) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Val80fs (c.237del) in the general population?

COG5 p.Val80fs (c.237del) is very rare (popmax 0.00668%, eas) (gnomAD).

How is COG5-CDG inherited?

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

COG5 p.Val80fs

c.237del · rs1330009938 · VCV932931

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

COG5-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,646 alleles · very rare

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.Val80fs
Coding: c.237del
MANE Select: NM_006348
dbSNP: rs1330009938
Type: Deletion
Location: chr7:107554340 (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.Arg723fs Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Cys33Valfs Pathogenic ★★ same condition
COG5 c.538+5del Uncertain significance ★★ same condition
COG5 p.Met825fs Uncertain significance ★★ same condition
COG5 c.1750-3del Benign/Likely benign ★★ same condition
COG5 c.538+20del Benign/Likely benign ★★ same condition
COG5 c.669+18_669+19del Benign ★★ same condition
COG5 c.1108+1_1108+2del 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-val80fs (accessed [today's date]).

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