Is COPA p.Ala176Val (c.527C>T) pathogenic?

COPA p.Ala176Val (c.527C>T) is classified Uncertain significance in COPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.0784); Very rare (popmax 0.00267%, afr); Associated with systemic lupus erythematosus, susceptibility to, 1.

What condition is associated with COPA p.Ala176Val (c.527C>T)?

COPA p.Ala176Val (c.527C>T) is associated with systemic lupus erythematosus, susceptibility to, 1, autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Ala176Val (c.527C>T) in the general population?

COPA p.Ala176Val (c.527C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about COPA p.Ala176Val (c.527C>T)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

COPA p.Ala176Val

c.527C>T · rs375464084 · VCV2739337

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

systemic lupus erythematosus, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	26.6	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 0.00267% African / African-American · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,613,990 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
European (non-Finnish)	0.000593%	168,572

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.Ala176Val
Coding: c.527C>T
MANE Select: NM_004371
dbSNP: rs375464084
Type: single nucleotide variant
Location: chr1:160325622 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB

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

Disease context

systemic lupus erythematosus, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune interstitial lung disease-arthritis syndrome

Similar variants

COPA p.Ala176= Likely benign ★ same residue
COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same condition
COPA p.Glu241Lys Pathogenic ★★ same condition
COPA p.Ala111Thr 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-ala176val (accessed [today's date]).

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