Is COG1 p.Arg38= (c.114G>C) pathogenic?

COG1 p.Arg38= (c.114G>C) is classified Likely benign in COG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Very rare (popmax 0.00391%, nfe); Associated with COG1-congenital disorder of glycosylation.

What condition is associated with COG1 p.Arg38= (c.114G>C)?

COG1 p.Arg38= (c.114G>C) is associated with COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Arg38= (c.114G>C) in the general population?

COG1 p.Arg38= (c.114G>C) is very rare (popmax 0.00391%, nfe) (gnomAD).

How is COG1-CDG inherited?

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

COG1 p.Arg38=

c.114G>C · VCV4804414

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00391%, nfe)

Conditions

COG1-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 0.73	GERP 3.1, phastCons 1
Overall
CADD	13.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00391% European (non-Finnish) · 46/1,177,860 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00268%

Overall 0.0033% 48/1,455,808 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00391%	25,606
Remaining individualsnot grpmax-eligible	0.00161%	62,248
South Asian	0.00111%	89,974

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.Arg38=
Coding: c.114G>C
MANE Select: NM_018714
Type: single nucleotide variant
Location: chr17:73193183 (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

COG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG1 p.Arg38Leu Uncertain significance ★ ⚠ same residue
COG1 c.1070+5G>A Pathogenic ★★ same condition
COG1 p.Arg336Ter Pathogenic ★★ same condition
COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same condition
COG1 p.Ala143Thr Uncertain significance ★★ same condition
COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val 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/cog1-p-arg38 (accessed [today's date]).

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