Is COG4 p.Arg515= (c.1545C>T) pathogenic?

COG4 p.Arg515= (c.1545C>T) is classified Likely benign in COG4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-10). Very rare (popmax 0.00878%, sas); Associated with COG4-related disorder.

What condition is associated with COG4 p.Arg515= (c.1545C>T)?

COG4 p.Arg515= (c.1545C>T) is associated with COG4-related disorder (ClinVar).

How common is COG4 p.Arg515= (c.1545C>T) in the general population?

COG4 p.Arg515= (c.1545C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

COG4 p.Arg515=

c.1545C>T · rs770365416 · VCV3051280

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

COG4-related disorder

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 -11	GERP -3.8
Overall
CADD	0.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,086 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00279% 45/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
African / African-American	0.00401%	24,966
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00271%	36,876

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: COG4
Protein: p.Arg515=
Coding: c.1545C>T
MANE Select: NM_015386
dbSNP: rs770365416
Type: single nucleotide variant
Location: chr16:70496368 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 1 PDB

Full COG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG4-related disorder

Similar variants

COG4 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
COG4 p.Arg468Gln Uncertain significance ★★ same condition
COG4 p.Gln311Ter Likely pathogenic ★ same condition
COG4 c.844+5G>C Uncertain significance ★ same condition
COG4 p.Asp778His Uncertain significance ★ same condition
COG4 p.Gly85Asp Uncertain significance ★ same condition
COG4 p.Thr680Pro Uncertain significance ★ same condition
COG4 p.Tyr50Phe 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/cog4-p-arg515 (accessed [today's date]).

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