Is COG8 p.Val496= (c.1488C>A) pathogenic?

COG8 p.Val496= (c.1488C>A) is classified Likely benign in COG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). Very rare (popmax 0.0022%, sas); Associated with COG8-congenital disorder of glycosylation.

What condition is associated with COG8 p.Val496= (c.1488C>A)?

COG8 p.Val496= (c.1488C>A) is associated with COG8-congenital disorder of glycosylation (ClinVar).

How common is COG8 p.Val496= (c.1488C>A) in the general population?

COG8 p.Val496= (c.1488C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

How is COG8-CDG inherited?

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

COG8 p.Val496=

c.1488C>A · rs759654404 · VCV1545023

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

COG8-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 3.4	GERP 0.46, phastCons 1
Overall
CADD	8.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000274% 4/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,544
European (non-Finnish)	0.000169%	590,012

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: COG8
Protein: p.Val496=
Coding: c.1488C>A
MANE Select: NM_032382
dbSNP: rs759654404
Type: single nucleotide variant
Location: chr16:69332808 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.67

Full COG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG8-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

COG8 c.1583-1G>A Pathogenic/Likely pathogenic ★★ same condition
COG8 p.Ala2Val Uncertain significance ★★ ⚠ same condition
COG8 p.Ala458Val Uncertain significance ★★ ⚠ same condition
COG8 p.Ala5Val Uncertain significance ★★ ⚠ same condition
COG8 p.Arg140Gln Uncertain significance ★★ ⚠ same condition
COG8 p.Arg244Lys Uncertain significance ★★ ⚠ same condition
COG8 p.Arg256Trp Uncertain significance ★★ ⚠ same condition
COG8 p.Arg450Cys 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/cog8-p-val496 (accessed [today's date]).

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