Is COG7 p.Arg568Pro (c.1703G>C) pathogenic?

COG7 p.Arg568Pro (c.1703G>C) is classified Uncertain significance in COG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). AlphaMissense: likely pathogenic (0.7214); Absent from gnomAD v4.1; Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Arg568Pro (c.1703G>C)?

COG7 p.Arg568Pro (c.1703G>C) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How common is COG7 p.Arg568Pro (c.1703G>C) in the general population?

COG7 p.Arg568Pro (c.1703G>C) is absent from gnomAD v4.1 (gnomAD).

How is COG7-CDG inherited?

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

What do computational predictors say about COG7 p.Arg568Pro (c.1703G>C)?

AlphaMissense predicts likely pathogenic (score 0.7214) — an in-silico prediction, not a clinical call.

COG7 p.Arg568Pro

c.1703G>C · VCV3681293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7214 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COG7-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.7214	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -13.54	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.017, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.033 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COG7
Protein: p.Arg568Pro
Coding: c.1703G>C
MANE Select: NM_153603
Type: single nucleotide variant
Location: chr16:23403794 (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 p.Arg568Ter Pathogenic ★ same residue
COG7 p.Arg568Gln Uncertain significance ★ ⚠ same residue
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

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-arg568pro (accessed [today's date]).

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