Is COPA p.Ile117Val (c.349A>G) pathogenic?

COPA p.Ile117Val (c.349A>G) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-22). AlphaMissense: likely benign (0.102); Very rare (popmax 0.000932%, nfe).

How common is COPA p.Ile117Val (c.349A>G) in the general population?

COPA p.Ile117Val (c.349A>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about COPA p.Ile117Val (c.349A>G)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

COPA p.Ile117Val

c.349A>G · rs2525459348 · VCV2499770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -6.93	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 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 11 kb · p 2.2e-12 · regional, not allelic
Overall
CADD	23.9	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 0.000932% European (non-Finnish) · 11/1,179,638 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000753% 11/1,461,208 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: COPA
Protein: p.Ile117Val
Coding: c.349A>G
MANE Select: NM_004371
dbSNP: rs2525459348
Type: single nucleotide variant
Location: chr1:160333640 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 117: 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-ile117val (accessed [today's date]).

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