Is CRPPA p.Leu449= (c.1345C>T) pathogenic?

CRPPA p.Leu449= (c.1345C>T) is classified Uncertain significance in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

What condition is associated with CRPPA p.Leu449= (c.1345C>T)?

CRPPA p.Leu449= (c.1345C>T) is associated with Congenital Muscular Dystrophy, alpha-dystroglycan related (ClinVar).

How common is CRPPA p.Leu449= (c.1345C>T) in the general population?

CRPPA p.Leu449= (c.1345C>T) is absent from gnomAD v4.1 (gnomAD).

CRPPA p.Leu449=

c.1345C>T · rs1781841579 · VCV909787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Congenital Muscular Dystrophy, alpha-dystroglycan related

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 3	phastCons 1
Overall
CADD	5.375	PHRED · no single calibrated threshold — expert panels disagree

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: CRPPA
Protein: p.Leu449=
Coding: c.1345C>T
MANE Select: NM_001101426
dbSNP: rs1781841579
Type: single nucleotide variant
Location: chr7:16091706 (GRCh38)
Gene constraint: LOEUF 1.462 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.63 · 1 PDB
Residue 449: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); a UniProt-annotated variant site (in mddgc7); a β-strand

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

Disease context

Congenital Muscular Dystrophy, alpha-dystroglycan related

Similar variants

CRPPA p.Arg205Cys Likely pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.1251+4G>A Uncertain significance ★★ same condition
CRPPA c.*2235A>C Uncertain significance ★★ same condition
CRPPA c.*2237A>G Uncertain significance ★★ same condition
CRPPA c.*2248C>T Uncertain significance ★★ same condition
CRPPA c.*2263A>C Uncertain significance ★★ same condition
CRPPA c.*2265A>G Uncertain significance ★★ same condition

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/crppa-p-leu449 (accessed [today's date]).

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