Is CRPPA p.Val371Ala (c.1112T>C) pathogenic?

CRPPA p.Val371Ala (c.1112T>C) is classified Uncertain significance in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.2072); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2U.

What condition is associated with CRPPA p.Val371Ala (c.1112T>C)?

CRPPA p.Val371Ala (c.1112T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2U, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (ClinVar).

How common is CRPPA p.Val371Ala (c.1112T>C) in the general population?

CRPPA p.Val371Ala (c.1112T>C) is absent from gnomAD v4.1 (gnomAD).

How is ISPD-related limb-girdle muscular dystrophy R20 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CRPPA p.Val371Ala (c.1112T>C)?

AlphaMissense predicts likely benign (score 0.2072) — an in-silico prediction, not a clinical call.

CRPPA p.Val371Ala

c.1112T>C · rs2546639338 · VCV2172733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2072 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2U

Computational evidence

Protein change
AlphaMissense	0.2072	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -10.83	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val371Ala
Coding: c.1112T>C
MANE Select: NM_001101426
dbSNP: rs2546639338
Type: single nucleotide variant
Location: chr7:16258397 (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 371: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); a β-strand

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2U — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

For ISPD-related limb-girdle muscular dystrophy R20 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CRPPA p.Val371= Likely benign ★ 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.Arg268Ter Pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.1026+5G>C 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-val371ala (accessed [today's date]).

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