Is COG7 p.Cys409= (c.1227C>T) pathogenic?

COG7 p.Cys409= (c.1227C>T) is classified Likely benign in COG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). Ultra-rare (popmax 0.028%, afr); Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Cys409= (c.1227C>T)?

COG7 p.Cys409= (c.1227C>T) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How common is COG7 p.Cys409= (c.1227C>T) in the general population?

COG7 p.Cys409= (c.1227C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

How is COG7-CDG inherited?

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

COG7 p.Cys409=

c.1227C>T · rs753240981 · VCV2746993

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Conditions

COG7-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 0.94	GERP -1.7, phastCons 0.099
Overall
CADD	9.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/74,926 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00248% 40/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,568
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.00119%	84,289

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: COG7
Protein: p.Cys409=
Coding: c.1227C>T
MANE Select: NM_153603
dbSNP: rs753240981
Type: single nucleotide variant
Location: chr16:23417032 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.77

Full COG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG7-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG7-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG7 c.318+1G>A Likely pathogenic ★★ same condition
COG7 p.Ala606Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COG7 p.Arg444Ter Pathogenic/Likely pathogenic ★★ same condition
COG7 c.1475+4G>A Uncertain significance ★★ same condition
COG7 p.Ala194Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala222Thr Uncertain significance ★★ ⚠ same condition
COG7 p.Ala29Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala325Thr 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/cog7-p-cys409 (accessed [today's date]).

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