Is COG2 p.Ser714fs (c.2139_2142del) pathogenic?

COG2 p.Ser714fs (c.21392142del) is classified Uncertain significance in COG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). Absent from gnomAD; Associated with congenital disorder of glycosylation, type IIq.

What condition is associated with COG2 p.Ser714fs (c.2139_2142del)?

COG2 p.Ser714fs (c.2139_2142del) is associated with congenital disorder of glycosylation, type IIq (ClinVar).

How common is COG2 p.Ser714fs (c.2139_2142del) in the general population?

COG2 p.Ser714fs (c.2139_2142del) is absent from gnomAD (gnomAD).

How is COG2-CDG inherited?

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

COG2 p.Ser714fs

c.2139_2142del · rs2527679257 · VCV2147512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital disorder of glycosylation, type IIq

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (18 of 18) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 0.56

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COG2
Protein: p.Ser714fs
Coding: c.2139_2142del
MANE Select: NM_007357
dbSNP: rs2527679257
Type: Deletion
Location: chr1:230693315 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38

Full COG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For COG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

COG2 p.Gln87fs Pathogenic ★ same condition
COG2 p.Lys503fs Pathogenic ★ same condition
COG2 c.235-8del Likely benign ★ same condition
COG2 p.Ala160Val Uncertain significance ★★ ⚠ same condition
COG2 p.Ala339Pro Uncertain significance ★★ ⚠ same condition
COG2 p.Arg138Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg241Gln Uncertain significance ★★ ⚠ same condition
COG2 p.Arg356Gln 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/cog2-p-ser714fs (accessed [today's date]).

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