Is CRPPA p.Glu292= (c.876A>G) pathogenic?

CRPPA p.Glu292= (c.876A>G) is classified Conflicting classifications of pathogenicity in CRPPA (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.087%, sas); Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

How common is CRPPA p.Glu292= (c.876A>G) in the general population?

CRPPA p.Glu292= (c.876A>G) is ultra-rare (popmax 0.087%, sas) (gnomAD).

CRPPA p.Glu292=

Q: What condition is associated with CRPPA p.Glu292= (c.876A>G)?

CRPPA p.Glu292= (c.876A>G) is associated with Congenital Muscular Dystrophy, alpha-dystroglycan related, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, autosomal recessive limb-girdle muscular dystrophy type 2U (ClinVar).

c.876A>G · rs371300262 · VCV514247

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.087%, sas)

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 1.8	GERP -1.9, phastCons 1
Overall
CADD	1.861	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.087% South Asian · 77/88,476 alleles

Filtering AF 0.0713% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0655%

Overall 0.0207% 329/1,586,306 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.609%	164
South Asiangrpmax	0.087%	1,149
Remaining individualsnot grpmax-eligible	0.0488%	2,048
Middle Eastern	0.0179%	5,602
Admixed American	0.00516%	19,366
European (non-Finnish)	0.00353%	28,336

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRPPA
Protein: p.Glu292=
Coding: c.876A>G
MANE Select: NM_001101426
dbSNP: rs371300262
Type: single nucleotide variant
Location: chr7:16278186 (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 292: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy)

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

Disease context

Congenital Muscular Dystrophy, alpha-dystroglycan related

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 autosomal recessive limb-girdle muscular dystrophy type 2U

Similar variants

CRPPA p.Glu292fs Pathogenic ★ same residue
CRPPA p.Glu292Arg Uncertain significance ★ same residue
CRPPA c.1120-1G>T Pathogenic ★★ same condition
CRPPA c.258-1G>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.835+2T>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA p.Arg184Ter Pathogenic ★★ same condition
CRPPA p.Arg205Cys Likely pathogenic ★★ same condition
CRPPA p.Arg268Ter Pathogenic ★★ 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-glu292 (accessed [today's date]).

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