Is COP1 p.Ala7Val (c.20C>T) pathogenic?

COP1 p.Ala7Val (c.20C>T) is classified Uncertain significance in COP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.1437); Ultra-rare (popmax 0.0182%, eas).

How common is COP1 p.Ala7Val (c.20C>T) in the general population?

COP1 p.Ala7Val (c.20C>T) is ultra-rare (popmax 0.0182%, eas) (gnomAD).

What do computational predictors say about COP1 p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1437) — an in-silico prediction, not a clinical call.

COP1 p.Ala7Val

c.20C>T · rs893191628 · VCV2542379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1437 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1437	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.38, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 396 bp · p 0.98 · regional, not allelic
Overall
CADD	16.75	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 0.0182% East Asian · 6/32,924 alleles

Filtering AF 0.00792% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00538%

Overall 0.00077% 11/1,428,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0182%	5,487
African / African-American	0.00446%	22,412
Admixed American	0.00288%	34,770
Remaining individualsnot grpmax-eligible	0.00184%	54,434

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_022457
dbSNP: rs893191628
Type: single nucleotide variant
Location: chr1:176206959 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 75.64 · 7 PDB
Residue 7: the 'disordered' region

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.Arg378Cys 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-ala7val (accessed [today's date]).

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