Is COG1 p.Val709Ile (c.2125G>A) pathogenic?

COG1 p.Val709Ile (c.2125G>A) is classified Uncertain significance in COG1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0659); Absent from gnomAD v4.1; Associated with prostate cancer.

What condition is associated with COG1 p.Val709Ile (c.2125G>A)?

COG1 p.Val709Ile (c.2125G>A) is associated with prostate cancer (ClinVar).

How common is COG1 p.Val709Ile (c.2125G>A) in the general population?

COG1 p.Val709Ile (c.2125G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COG1 p.Val709Ile (c.2125G>A)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

COG1 p.Val709Ile

c.2125G>A · rs193920973 · VCV161723

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.2	GERP -1.7, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	11.07	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

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.Val709Ile
Coding: c.2125G>A
MANE Select: NM_018714
dbSNP: rs193920973
Type: single nucleotide variant
Location: chr17:73203051 (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

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COG1 p.Gln450Ter Uncertain significance same condition
COG1 c.1070+5G>A Pathogenic ★★ same type
COG1 p.Arg336Ter Pathogenic ★★ same type
COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same type
COG1 p.Ala143Thr Uncertain significance ★★ ⚠ same type
COG1 p.Ala209Val Uncertain significance ★★ ⚠ same type
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same type
COG1 p.Ala380Val Uncertain significance ★★ ⚠ same type

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-val709ile (accessed [today's date]).

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