Is COG2 p.Ser363= (c.1089T>C) pathogenic?

COG2 p.Ser363= (c.1089T>C) is classified Likely benign in COG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-01). Very rare (popmax 8.48e-05%, nfe).

How common is COG2 p.Ser363= (c.1089T>C) in the general population?

COG2 p.Ser363= (c.1089T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

COG2 p.Ser363=

c.1089T>C · rs1387051453 · VCV1176856

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -1.2	GERP 1.2, phastCons 0.002
Overall
CADD	7.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,688 alleles

Overall 6.84e-05% 1/1,461,490 alleles · very rare

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: COG2
Protein: p.Ser363=
Coding: c.1089T>C
MANE Select: NM_007357
dbSNP: rs1387051453
Type: single nucleotide variant
Location: chr1:230678975 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38

Full COG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COG2 p.Ala160Val Uncertain significance ★★ ⚠ same type
COG2 p.Ala339Pro Uncertain significance ★★ ⚠ same type
COG2 p.Arg138Gln Uncertain significance ★★ ⚠ same type
COG2 p.Arg241Gln Uncertain significance ★★ ⚠ same type
COG2 p.Arg356Gln Uncertain significance ★★ ⚠ same type
COG2 p.Arg356Trp Uncertain significance ★★ ⚠ same type
COG2 p.Arg39Gln Uncertain significance ★★ ⚠ same type
COG2 p.Arg39Trp 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/cog2-p-ser363 (accessed [today's date]).

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