Is COP1 p.Val703= (c.2109G>A) pathogenic?

COP1 p.Val703= (c.2109G>A) is classified Likely benign in COP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-31). Very rare (popmax 6.87e-05%).

How common is COP1 p.Val703= (c.2109G>A) in the general population?

COP1 p.Val703= (c.2109G>A) is very rare (popmax 6.87e-05%) (gnomAD).

COP1 p.Val703=

c.2109G>A · rs1571414351 · VCV756996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -0.4, phastCons 0.92
Overall
CADD	6.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.87e-05%

Overall 6.87e-05% 1/1,454,590 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: COP1
Protein: p.Val703=
Coding: c.2109G>A
MANE Select: NM_022457
dbSNP: rs1571414351
Type: single nucleotide variant
Location: chr1:175986967 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 75.64 · 7 PDB
Residue 703: a β-strand

Full COP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COP1 c.1142-7C>T Likely benign ★★ same type
COP1 p.Arg295Thr Benign ★★ ⚠ same type
COP1 p.Met299Val Benign ★★ same type
COP1 p.Ala117Val Uncertain significance ★ ⚠ same type
COP1 p.Ala12Ser Uncertain significance ★ ⚠ same type
COP1 p.Ala354Val Uncertain significance ★ ⚠ same type
COP1 p.Ala457Val Uncertain significance ★ ⚠ same type
COP1 p.Ala7Val 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/cop1-p-val703 (accessed [today's date]).

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