Is COG1 p.Lys828Glu (c.2482A>G) pathogenic?

COG1 p.Lys828Glu (c.2482A>G) is classified Uncertain significance in COG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2564); Ultra-rare (popmax 0.035%, amr); Associated with Inborn genetic diseases.

What condition is associated with COG1 p.Lys828Glu (c.2482A>G)?

COG1 p.Lys828Glu (c.2482A>G) is associated with Inborn genetic diseases, COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Lys828Glu (c.2482A>G) in the general population?

COG1 p.Lys828Glu (c.2482A>G) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about COG1 p.Lys828Glu (c.2482A>G)?

AlphaMissense predicts likely benign (score 0.2564) — an in-silico prediction, not a clinical call.

COG1 p.Lys828Glu

c.2482A>G · rs1011259443 · VCV889029

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2564 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2564	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/60,004 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00186% 30/1,613,810 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
Remaining individualsnot grpmax-eligible	0.0112%	8,923
African / African-American	0.00267%	37,455

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: COG1
Protein: p.Lys828Glu
Coding: c.2482A>G
MANE Select: NM_018714
dbSNP: rs1011259443
Type: single nucleotide variant
Location: chr17:73205652 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.82

Full COG1 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

Also linked: COG1-congenital disorder of glycosylation

Similar variants

COG1 p.Lys828= Likely benign ★ same residue
COG1 c.1070+5G>A Pathogenic ★★ same condition
COG1 p.Arg336Ter Pathogenic ★★ same condition
COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same condition
COG1 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val 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/cog1-p-lys828glu (accessed [today's date]).

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