Is COG6 p.Pro290= (c.870C>T) pathogenic?

COG6 p.Pro290= (c.870C>T) is classified Likely benign in COG6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-09). Ultra-rare (popmax 0.0164%, mid); Associated with COG6-congenital disorder of glycosylation.

What condition is associated with COG6 p.Pro290= (c.870C>T)?

COG6 p.Pro290= (c.870C>T) is associated with COG6-congenital disorder of glycosylation, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (ClinVar).

How common is COG6 p.Pro290= (c.870C>T) in the general population?

COG6 p.Pro290= (c.870C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is COG6-CGD inherited?

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

COG6 p.Pro290=

c.870C>T · rs145427916 · VCV2932526

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.008	GERP -3.6, phastCons 0.046
Overall
CADD	7.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00186% 30/1,613,520 alleles · ultra-rare exomes 26/1,461,860 · genomes 4/151,660 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.012%	8,302
Admixed American	0.00334%	29,959
Finnishnot grpmax-eligible	0.00313%	31,986
European (non-Finnish)	0.00136%	73,748

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.Pro290=
Coding: c.870C>T
MANE Select: NM_020751
dbSNP: rs145427916
Type: single nucleotide variant
Location: chr13:39687584 (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 p.Pro290Ser Uncertain significance ★ ⚠ same residue
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

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-pro290 (accessed [today's date]).

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