Is COG5 p.Thr561= (c.1683A>G) pathogenic?

COG5 p.Thr561= (c.1683A>G) is classified Benign in COG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-21). Rare (popmax 0.401%, afr); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Thr561= (c.1683A>G)?

COG5 p.Thr561= (c.1683A>G) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Thr561= (c.1683A>G) in the general population?

COG5 p.Thr561= (c.1683A>G) is rare (popmax 0.401%, afr) (gnomAD).

How is COG5-CDG inherited?

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

COG5 p.Thr561=

c.1683A>G · rs140610590 · VCV771683

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.401%, afr)

Conditions

COG5-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 1.5	GERP 1.6, phastCons 1
Overall
CADD	9.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.401% African / African-American · 298/74,322 alleles

Filtering AF 0.363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.349%

Overall 0.0215% 340/1,581,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.401%	249
Middle Eastern	0.0333%	3,004
Admixed American	0.0301%	3,327
Remaining individualsnot grpmax-eligible	0.0261%	3,837
South Asian	0.00111%	90,378
European (non-Finnish)	0.000435%	230,059

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: COG5
Protein: p.Thr561=
Coding: c.1683A>G
MANE Select: NM_006348
dbSNP: rs140610590
Type: single nucleotide variant
Location: chr7:107258276 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37

Full COG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG5-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG5-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

COG5 p.Thr561Ala Uncertain significance ★ ⚠ same residue
COG5 c.1475+1G>A Likely pathogenic ★★ same condition
COG5 c.2295+2T>C Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg205Ter Pathogenic ★★ same condition
COG5 p.Arg283Ter Pathogenic ★★ same condition
COG5 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg690Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg708Ter Pathogenic/Likely pathogenic ★★ 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/cog5-p-thr561 (accessed [today's date]).

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