Is COG6 p.Phe414= (c.1242C>T) pathogenic?

COG6 p.Phe414= (c.1242C>T) is classified Likely benign in COG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-11). Absent from gnomAD v4.1; Associated with COG6-congenital disorder of glycosylation.

What condition is associated with COG6 p.Phe414= (c.1242C>T)?

COG6 p.Phe414= (c.1242C>T) is associated with COG6-congenital disorder of glycosylation, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (ClinVar).

How common is COG6 p.Phe414= (c.1242C>T) in the general population?

COG6 p.Phe414= (c.1242C>T) is absent from gnomAD v4.1 (gnomAD).

How is COG6-CGD inherited?

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

COG6 p.Phe414=

c.1242C>T · rs2138033067 · VCV1157643

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,914)

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 1.8	GERP 0.85, phastCons 1
Overall
CADD	10.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,572,914). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COG6
Protein: p.Phe414=
Coding: c.1242C>T
MANE Select: NM_020751
dbSNP: rs2138033067
Type: single nucleotide variant
Location: chr13:39699576 (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.Phe414fs Pathogenic 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-phe414 (accessed [today's date]).

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