Is COPA p.Val1062Leu (c.3184G>T) pathogenic?

COPA p.Val1062Leu (c.3184G>T) is classified Conflicting classifications of pathogenicity in COPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2084); Ultra-rare (popmax 0.0545%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Val1062Leu (c.3184G>T)?

COPA p.Val1062Leu (c.3184G>T) is associated with Inborn genetic diseases, autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Val1062Leu (c.3184G>T) in the general population?

COPA p.Val1062Leu (c.3184G>T) is ultra-rare (popmax 0.0545%, nfe) (gnomAD).

What do computational predictors say about COPA p.Val1062Leu (c.3184G>T)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

COPA p.Val1062Leu

c.3184G>T · rs138625189 · VCV583053

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0545%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -4.08	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 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	20.7	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

Grpmax group 0.0545% European (non-Finnish) · 643/1,180,036 alleles

Filtering AF 0.051% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.0422% 681/1,614,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0545%	1,835
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Finnishnot grpmax-eligible	0.0234%	4,268
African / African-American	0.00533%	18,758
Admixed American	0.005%	20,009

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: COPA
Protein: p.Val1062Leu
Coding: c.3184G>T
MANE Select: NM_004371
dbSNP: rs138625189
Type: single nucleotide variant
Location: chr1:160291893 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1062: an α-helix

Full COPA 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

Also linked: autoimmune interstitial lung disease-arthritis syndrome

Similar variants

COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same condition
COPA p.Glu241Lys Pathogenic ★★ same condition
COPA p.Ala111Thr Uncertain significance ★★ ⚠ same condition
COPA p.Ala176Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala407Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala422Thr Uncertain significance ★★ ⚠ same condition
COPA p.Ala469Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala510Thr 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/copa-p-val1062leu (accessed [today's date]).

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