Is COG1 p.Ser942Phe (c.2825C>T) pathogenic?

COG1 p.Ser942Phe (c.2825C>T) is classified Uncertain significance in COG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-05). AlphaMissense: likely benign (0.1149); Very rare (popmax 8.47e-05%, nfe); Associated with COG1-congenital disorder of glycosylation.

What condition is associated with COG1 p.Ser942Phe (c.2825C>T)?

COG1 p.Ser942Phe (c.2825C>T) is associated with COG1-congenital disorder of glycosylation (ClinVar).

How common is COG1 p.Ser942Phe (c.2825C>T) in the general population?

COG1 p.Ser942Phe (c.2825C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is COG1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COG1 p.Ser942Phe (c.2825C>T)?

AlphaMissense predicts likely benign (score 0.1149) — an in-silico prediction, not a clinical call.

COG1 p.Ser942Phe

c.2825C>T · rs2511092504 · VCV2809614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1149	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 0.73
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	20.5	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 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 6.84e-05% 1/1,461,662 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: COG1
Protein: p.Ser942Phe
Coding: c.2825C>T
MANE Select: NM_001098832 · reported on NM_018714
dbSNP: rs2511092504
Type: single nucleotide variant
Location: chr17:73208333 (GRCh38)

Full COG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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-ser942phe (accessed [today's date]).

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