Is CPA5 p.Val382= (c.1146C>T) pathogenic?

CPA5 p.Val382= (c.1146C>T) is classified Likely benign in CPA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Very rare (popmax 0.00801%, afr).

How common is CPA5 p.Val382= (c.1146C>T) in the general population?

CPA5 p.Val382= (c.1146C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

CPA5 p.Val382=

c.1146C>T · VCV4233142

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.057	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -5.2
Overall
CADD	0.621	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,904 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00112% 18/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,484
South Asian	0.00439%	22,770
Admixed American	0.00167%	59,978
European (non-Finnish)	0.000593%	168,573

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: CPA5
Protein: p.Val382=
Coding: c.1146C>T
MANE Select: NM_080385
Type: single nucleotide variant
Location: chr7:130368432 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.56
Residue 382: the peptidase m14 domain

Full CPA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPA5 p.Val382Ile Uncertain significance ★ ⚠ same residue
CPA5 p.Ala120Thr Uncertain significance ★ ⚠ same type
CPA5 p.Ala188Val Uncertain significance ★ ⚠ same type
CPA5 p.Ala229Val Uncertain significance ★ ⚠ same type
CPA5 p.Ala350Asp Uncertain significance ★ ⚠ same type
CPA5 p.Ala356Val Uncertain significance ★ ⚠ same type
CPA5 p.Ala393Asp Uncertain significance ★ ⚠ same type
CPA5 p.Ala393Thr 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/cpa5-p-val382 (accessed [today's date]).

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