Is CPA3 p.Val149= (c.447T>G) pathogenic?

CPA3 p.Val149= (c.447T>G) is classified Likely benign in CPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-13). Ultra-rare (popmax 0.0129%, nfe).

How common is CPA3 p.Val149= (c.447T>G) in the general population?

CPA3 p.Val149= (c.447T>G) is ultra-rare (popmax 0.0129%, nfe) (gnomAD).

CPA3 p.Val149=

c.447T>G · rs367753806 · VCV740759

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0129%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.58, phastCons 0.31
Overall
CADD	5.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0129% European (non-Finnish) · 151/1,171,182 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00992% 159/1,603,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0129%	7,756
Remaining individualsnot grpmax-eligible	0.00966%	10,348
Admixed American	0.00167%	59,776
African / African-American	0.00134%	74,684

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: CPA3
Protein: p.Val149=
Coding: c.447T>G
MANE Select: NM_016352 · reported on NM_001870
dbSNP: rs367753806
Type: single nucleotide variant
Location: chr3:148878721 (GRCh38)
Structure: AlphaFold pLDDT 93.88 · 5 PDB
Residue 149: the peptidase m14 domain; a β-strand

Full CPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPA3 p.Arg273Pro Benign ★★ same type
CPA3 p.Thr283Met Benign ★★ ⚠ same type
CPA3 p.Ala117Thr Uncertain significance ★ ⚠ same type
CPA3 p.Ala15Thr Uncertain significance ★ ⚠ same type
CPA3 p.Ala177Thr Uncertain significance ★ ⚠ same type
CPA3 p.Ala56Thr Uncertain significance ★ ⚠ same type
CPA3 p.Ala77Thr Uncertain significance ★ ⚠ same type
CPA3 p.Arg20His 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/cpa3-p-val149 (accessed [today's date]).

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