Is COG6 p.Asp243= (c.729C>T) pathogenic?

COG6 p.Asp243= (c.729C>T) is classified Conflicting classifications of pathogenicity in COG6 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.215%, afr); Associated with COG6-congenital disorder of glycosylation.

What condition is associated with COG6 p.Asp243= (c.729C>T)?

COG6 p.Asp243= (c.729C>T) is associated with COG6-congenital disorder of glycosylation, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (ClinVar).

How common is COG6 p.Asp243= (c.729C>T) in the general population?

COG6 p.Asp243= (c.729C>T) is rare (popmax 0.215%, afr) (gnomAD).

How is COG6-CGD inherited?

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

COG6 p.Asp243=

c.729C>T · rs117688574 · VCV312137

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.215%, afr)

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 -0.21	GERP -3.6
Overall
CADD	2.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% African / African-American · 161/74,938 alleles

Filtering AF 0.188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.177%

Overall 0.204% 3,291/1,612,024 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.44%	41
Remaining individualsnot grpmax-eligible	0.277%	361
African / African-Americangrpmax	0.215%	465
European (non-Finnish)	0.182%	550
Admixed American	0.132%	759
Middle Eastern	0.0661%	1,513
South Asian	0.00769%	13,004
Finnishnot grpmax-eligible	0.00313%	31,999
East Asian	0.00223%	44,802

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp243=
Coding: c.729C>T
MANE Select: NM_020751
dbSNP: rs117688574
Type: single nucleotide variant
Location: chr13:39682205 (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-asp243 (accessed [today's date]).

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