Is COG8 p.Arg600Ter (c.1798C>T) pathogenic?

COG8 p.Arg600Ter (c.1798C>T) is classified Uncertain significance in COG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Very rare (popmax 0.00119%, sas); Associated with COG8-related disorder.

What condition is associated with COG8 p.Arg600Ter (c.1798C>T)?

COG8 p.Arg600Ter (c.1798C>T) is associated with COG8-related disorder (ClinVar).

How common is COG8 p.Arg600Ter (c.1798C>T) in the general population?

COG8 p.Arg600Ter (c.1798C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

COG8 p.Arg600Ter

c.1798C>T · rs1156701509 · VCV2628825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

COG8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.93	GERP 0.58, phastCons 0.001
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,056 alleles

Overall 0.000129% 2/1,546,826 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,056
European (non-Finnish)	8.73e-05%	1,145,872

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.Arg600Ter
Coding: c.1798C>T
MANE Select: NM_032382
dbSNP: rs1156701509
Type: single nucleotide variant
Location: chr16:69330880 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.67
Residue 600: the 'disordered' region

Full COG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG8-related disorder

Similar variants

COG8 p.Arg600Gln Uncertain significance ★ ⚠ same residue
COG8 p.Arg183Ter Likely pathogenic ★ same condition
COG8 p.Glu560fs Pathogenic/Likely pathogenic ★★ same condition
COG8 p.Phe563fs Likely pathogenic ★★ same condition
COG8 c.1583-1G>A Pathogenic/Likely pathogenic ★★ same type
COG8 p.Ala16Gly Uncertain significance ★★ ⚠ same type
COG8 p.Ala2Val Uncertain significance ★★ ⚠ same type
COG8 p.Ala458Val Uncertain significance ★★ ⚠ same type

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-arg600ter (accessed [today's date]).

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