Is COG5 p.Arg387Pro (c.1160G>C) pathogenic?

COG5 p.Arg387Pro (c.1160G>C) is classified Uncertain significance in COG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.9835); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COG5 p.Arg387Pro (c.1160G>C)?

COG5 p.Arg387Pro (c.1160G>C) is associated with Inborn genetic diseases (ClinVar).

How common is COG5 p.Arg387Pro (c.1160G>C) in the general population?

COG5 p.Arg387Pro (c.1160G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COG5 p.Arg387Pro (c.1160G>C)?

AlphaMissense predicts likely pathogenic (score 0.9835) — an in-silico prediction, not a clinical call.

COG5 p.Arg387Pro

c.1160G>C · rs35258567 · VCV2487869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9835	likely pathogenic · top 3% in COG5
REVEL	0.7	pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 0.93, phastCons 0.36
Regional constraint	o/e 1.09	unconstrained · MANE · 360 kb · p 0.0042 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R418P vs ClinVar R387P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COG5
Protein: p.Arg387Pro
Coding: c.1160G>C
MANE Select: NM_006348
dbSNP: rs35258567
Type: single nucleotide variant
Location: chr7:107298295 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COG5 p.Arg387Cys Uncertain significance ★ ⚠ same residue
COG5 p.Arg387His Conflicting classifications of pathogenicity ★ ⚠ same residue
COG5 p.Tyr416Ter Pathogenic ★★ same condition
COG5 c.-25C>A Uncertain significance ★★ ⚠ same condition
COG5 p.Ala15Gly Uncertain significance ★★ ⚠ same condition
COG5 p.Ala20Val Uncertain significance ★★ ⚠ same condition
COG5 p.Ala263Thr Uncertain significance ★★ ⚠ same condition
COG5 p.Ala409Thr 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/cog5-p-arg387pro (accessed [today's date]).

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