Is COG6 p.Ser241= (c.723A>G) pathogenic?

COG6 p.Ser241= (c.723A>G) is classified Likely benign in COG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-27). Very rare (popmax 6.85e-05%); Associated with COG6-congenital disorder of glycosylation.

What condition is associated with COG6 p.Ser241= (c.723A>G)?

COG6 p.Ser241= (c.723A>G) is associated with COG6-congenital disorder of glycosylation, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (ClinVar).

How common is COG6 p.Ser241= (c.723A>G) in the general population?

COG6 p.Ser241= (c.723A>G) is very rare (popmax 6.85e-05%) (gnomAD).

How is COG6-CGD inherited?

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

COG6 p.Ser241=

c.723A>G · rs2500584041 · VCV1951953

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Conditions

COG6-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 -0.88	GERP -3.6
Overall
CADD	4.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,852 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: COG6
Protein: p.Ser241=
Coding: c.723A>G
MANE Select: NM_020751
dbSNP: rs2500584041
Type: single nucleotide variant
Location: chr13:39682199 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.62

Full COG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG6-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

For COG6-CGD (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

COG6 c.1167-24A>G Pathogenic/Likely pathogenic ★★ same condition
COG6 p.Arg171Ter Pathogenic ★★ same condition
COG6 p.Arg360Ter Pathogenic/Likely pathogenic ★★ same condition
COG6 p.Leu512Ter Pathogenic/Likely pathogenic ★★ same condition
COG6 c.*1532T>G Uncertain significance ★★ same condition
COG6 c.*52G>A Uncertain significance ★★ same condition
COG6 p.Ala13Thr Uncertain significance ★★ ⚠ same condition
COG6 p.Arg121His 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/cog6-p-ser241 (accessed [today's date]).

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