Is CPA1 p.Ser282Pro (c.844T>C) pathogenic?

CPA1 p.Ser282Pro (c.844T>C) is classified Pathogenic in CPA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9837); Absent from gnomAD v4.1; Associated with CPA1-related disorder.

What condition is associated with CPA1 p.Ser282Pro (c.844T>C)?

CPA1 p.Ser282Pro (c.844T>C) is associated with CPA1-related disorder (ClinVar).

How common is CPA1 p.Ser282Pro (c.844T>C) in the general population?

CPA1 p.Ser282Pro (c.844T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPA1 p.Ser282Pro (c.844T>C)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

CPA1 p.Ser282Pro

c.844T>C · rs781820716 · VCV2136614

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CPA1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic ✓ concordant with ClinVar · top 3% in CPA1
REVEL	0.587	indeterminate
SaProt	LLR -16.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.88	unconstrained · MANE · 7,487 bp · p 0.0037 · regional, not allelic
Overall
CADD	27.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPA1
Protein: p.Ser282Pro
Coding: c.844T>C
MANE Select: NM_001868
dbSNP: rs781820716
Type: single nucleotide variant
Location: chr7:130385202 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.41 · 6 PDB
Residue 282: the peptidase m14 domain

Full CPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPA1-related disorder

Similar variants

CPA1 p.Ser282Cys Uncertain significance ★★ ⚠ same residue
CPA1 p.Ser282= Likely benign ★★ same residue
CPA1 p.Ser282Phe Uncertain significance ★ ⚠ same residue
CPA1 p.Arg382Trp Uncertain significance ★★ ⚠ same condition
CPA1 p.Asn256Lys Likely pathogenic ★★ same type
CPA1 c.1072+1G>T Uncertain significance ★★ same type
CPA1 c.1073-1G>A Uncertain significance ★★ same type
CPA1 c.147+4A>C 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/cpa1-p-ser282pro (accessed [today's date]).

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