Is CRPPA p.Thr316= (c.948A>G) pathogenic?

CRPPA p.Thr316= (c.948A>G) is classified Conflicting classifications of pathogenicity in CRPPA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00391%, nfe); Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

How common is CRPPA p.Thr316= (c.948A>G) in the general population?

CRPPA p.Thr316= (c.948A>G) is very rare (popmax 0.00391%, nfe) (gnomAD).

CRPPA p.Thr316=

Q: What condition is associated with CRPPA p.Thr316= (c.948A>G)?

CRPPA p.Thr316= (c.948A>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.948A>G · rs780620823 · VCV288383

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00391%, nfe)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP 0.24	GERP 3.9, phastCons 0.54
Overall
CADD	5.658	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00391% European (non-Finnish) · 46/1,177,610 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00268%

Overall 0.00286% 46/1,609,600 alleles · very rare

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.Thr316=
Coding: c.948A>G
dbSNP: rs780620823
Type: single nucleotide variant
Location: chr7:16258998 (GRCh38)

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

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-thr316 (accessed [today's date]).

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