Is COG8 p.Ile7Ser (c.20T>G) pathogenic?

COG8 p.Ile7Ser (c.20T>G) is classified Likely benign in COG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0834); Rare (popmax 0.495%, afr); Associated with COG8-congenital disorder of glycosylation.

What condition is associated with COG8 p.Ile7Ser (c.20T>G)?

COG8 p.Ile7Ser (c.20T>G) is associated with COG8-congenital disorder of glycosylation (ClinVar).

How common is COG8 p.Ile7Ser (c.20T>G) in the general population?

COG8 p.Ile7Ser (c.20T>G) is rare (popmax 0.495%, afr) (gnomAD).

How is COG8-CDG inherited?

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

What do computational predictors say about COG8 p.Ile7Ser (c.20T>G)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

COG8 p.Ile7Ser

c.20T>G · rs148609307 · VCV715279

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.495%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COG8-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -3.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP -4.6
Regional constraint	o/e 0.97	unconstrained · MANE · 8,710 bp · p 0.33 · regional, not allelic
Overall
CADD	5.592	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.495% African / African-American · 371/74,984 alleles

Filtering AF 0.453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.437%

Overall 0.028% 451/1,608,660 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.495%	202
Middle Eastern	0.0445%	2,248
Admixed American	0.0417%	2,401
Remaining individualsnot grpmax-eligible	0.0353%	2,830
European (non-Finnish)	0.00263%	38,062

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.Ile7Ser
Coding: c.20T>G
MANE Select: NM_032382
dbSNP: rs148609307
Type: single nucleotide variant
Location: chr16:69339533 (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 p.Ile7Val Conflicting classifications of pathogenicity ★ ⚠ same residue
PDF p.Ala7Pro Uncertain significance ★ ⚠ same residue
PDF p.Ala7Ser Uncertain significance ★ ⚠ same residue
PDF p.Ala7= Likely benign ★ same residue
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

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-ile7ser (accessed [today's date]).

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