Is COG1 p.Glu112del (c.334_336del) pathogenic?

COG1 p.Glu112del (c.334336del) is classified Uncertain significance in COG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-20). Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with COG1 p.Glu112del (c.334_336del)?

COG1 p.Glu112del (c.334_336del) is associated with Inborn genetic diseases, COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Glu112del (c.334_336del) in the general population?

COG1 p.Glu112del (c.334_336del) is very rare (popmax 0.00891%, eas) (gnomAD).

COG1 p.Glu112del

c.334_336del · rs749016283 · VCV1957672

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 5.7, phastCons 1
Overall
CADD	16.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,902 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000496% 8/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,225
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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.Glu112del
Coding: c.334_336del
MANE Select: NM_018714
dbSNP: rs749016283
Type: Deletion
Location: chr17:73196523 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: COG1-congenital disorder of glycosylation

Similar variants

COG1 c.2729+3_2729+9del Uncertain significance ★★ same condition
COG1 c.2221-14_2221-13del Benign/Likely benign ★★ same condition
COG1 p.Arg889fs Pathogenic ★ same condition
COG1 p.Asn364fs Pathogenic ★ same condition
COG1 p.Gln139fs Likely pathogenic ★ same condition
COG1 p.Gln908fs Likely pathogenic ★ same condition
COG1 p.Gly496fs Pathogenic ★ same condition
COG1 p.Lys113fs 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/cog1-p-glu112del (accessed [today's date]).

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