Is COG5 p.Thr292= (c.876T>G) pathogenic?

COG5 p.Thr292= (c.876T>G) is classified Benign/Likely benign in COG5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.86%, afr); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Thr292= (c.876T>G)?

COG5 p.Thr292= (c.876T>G) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Thr292= (c.876T>G) in the general population?

COG5 p.Thr292= (c.876T>G) is low-frequency (popmax 2.86%, afr) (gnomAD).

How is COG5-CDG inherited?

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

COG5 p.Thr292=

c.876T>G · rs74522314 · VCV358465

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.86%, 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 -0.33	GERP 2.1, phastCons 0.001
Overall
CADD	7.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.86% African / African-American · 2,144/74,992 alleles

Filtering AF 2.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.72%

Overall 0.174% 2,802/1,613,910 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.86%	35
Middle Eastern	0.346%	289
Admixed American	0.293%	341
Remaining individualsnot grpmax-eligible	0.288%	347
European (non-Finnish)	0.0236%	4,229
South Asian	0.0022%	45,539

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.Thr292=
Coding: c.876T>G
MANE Select: NM_006348
dbSNP: rs74522314
Type: single nucleotide variant
Location: chr7:107362380 (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

GPR22 p.Ile292Thr 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-thr292 (accessed [today's date]).

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