Is COG1 p.Ile510= (c.1530C>T) pathogenic?

COG1 p.Ile510= (c.1530C>T) is classified Likely benign in COG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-08). Very rare (popmax 0.004%, afr); Associated with COG1-congenital disorder of glycosylation.

What condition is associated with COG1 p.Ile510= (c.1530C>T)?

COG1 p.Ile510= (c.1530C>T) is associated with COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Ile510= (c.1530C>T) in the general population?

COG1 p.Ile510= (c.1530C>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is COG1-CDG inherited?

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

COG1 p.Ile510=

c.1530C>T · rs138661086 · VCV2956499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

COG1-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 -6.4	GERP -3.2
Overall
CADD	0.197	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,054 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000342% 5/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,018
Admixed American	0.00333%	30,011

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: COG1
Protein: p.Ile510=
Coding: c.1530C>T
MANE Select: NM_018714
dbSNP: rs138661086
Type: single nucleotide variant
Location: chr17:73201357 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.82

Full COG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG1 c.1070+5G>A Pathogenic ★★ same condition
COG1 p.Arg336Ter Pathogenic ★★ same condition
COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same condition
COG1 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala385Thr 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/cog1-p-ile510 (accessed [today's date]).

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