Is COG1 p.Phe173Cys (c.518T>G) pathogenic?

COG1 p.Phe173Cys (c.518T>G) is classified Uncertain significance in COG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.8782); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COG1 p.Phe173Cys (c.518T>G)?

COG1 p.Phe173Cys (c.518T>G) is associated with Inborn genetic diseases (ClinVar).

How common is COG1 p.Phe173Cys (c.518T>G) in the general population?

COG1 p.Phe173Cys (c.518T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COG1 p.Phe173Cys (c.518T>G)?

AlphaMissense predicts likely pathogenic (score 0.8782) — an in-silico prediction, not a clinical call.

COG1 p.Phe173Cys

c.518T>G · VCV4004816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8782	likely pathogenic · top 8% in COG1
REVEL	0.51	indeterminate
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

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

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: COG1
Protein: p.Phe173Cys
Coding: c.518T>G
MANE Select: NM_018714
Type: single nucleotide variant
Location: chr17:73196709 (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

Similar variants

COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala385Thr Uncertain significance ★★ ⚠ same condition
COG1 p.Ala563Val Uncertain significance ★★ ⚠ same condition
COG1 p.Arg165Gln Uncertain significance ★★ ⚠ same condition
COG1 p.Arg172Trp Uncertain significance ★★ ⚠ same condition
COG1 p.Arg178Gln 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-phe173cys (accessed [today's date]).

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