Is COPA p.Gln142His (c.426G>T) pathogenic?

COPA p.Gln142His (c.426G>T) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-13). AlphaMissense: likely benign (0.2761); Very rare (popmax 0.00223%, eas).

How common is COPA p.Gln142His (c.426G>T) in the general population?

COPA p.Gln142His (c.426G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COPA p.Gln142His (c.426G>T)?

AlphaMissense predicts likely benign (score 0.2761) — an in-silico prediction, not a clinical call.

COPA p.Gln142His

c.426G>T · rs1647575421 · VCV1304358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2761	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP -0.17, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	24.3	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 0.00223% East Asian · 1/44,862 alleles

Overall 0.000137% 2/1,461,490 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
European (non-Finnish)	8.48e-05%	1,179,916

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.Gln142His
Coding: c.426G>T
MANE Select: NM_004371
dbSNP: rs1647575421
Type: single nucleotide variant
Location: chr1:160332518 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 142: a β-strand

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

Similar variants

COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same type
COPA p.Glu241Lys Pathogenic ★★ same type
COPA p.Ala111Thr Uncertain significance ★★ ⚠ same type
COPA p.Ala176Val Uncertain significance ★★ ⚠ same type
COPA p.Ala407Val Uncertain significance ★★ ⚠ same type
COPA p.Ala422Thr Uncertain significance ★★ ⚠ same type
COPA p.Ala469Val Uncertain significance ★★ ⚠ same type
COPA p.Ala510Thr 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/copa-p-gln142his (accessed [today's date]).

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