Is COG6 p.Val8= (c.24G>A) pathogenic?

COG6 p.Val8= (c.24G>A) is classified Likely benign in COG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Absent from gnomAD v4.1; Associated with hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome.

How common is COG6 p.Val8= (c.24G>A) in the general population?

COG6 p.Val8= (c.24G>A) is absent from gnomAD v4.1 (gnomAD).

COG6 p.Val8=

Q: What condition is associated with COG6 p.Val8= (c.24G>A)?

COG6 p.Val8= (c.24G>A) is associated with hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, COG6-congenital disorder of glycosylation (ClinVar).

Q: How is Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome inherited?

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

c.24G>A · rs2500518447 · VCV2024219

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 1,595,618)

Conditions

hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

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 -1.9
Overall
CADD	6.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,595,618). 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.Val8=
Coding: c.24G>A
MANE Select: NM_020751
dbSNP: rs2500518447
Type: single nucleotide variant
Location: chr13:39655750 (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

hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: COG6-congenital disorder of glycosylation

For Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, 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-val8 (accessed [today's date]).

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