Is CRPPA p.Ile183Val (c.547A>G) pathogenic?

CRPPA p.Ile183Val (c.547A>G) is classified Uncertain significance in CRPPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-24). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00538%, afr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7.

How common is CRPPA p.Ile183Val (c.547A>G) in the general population?

CRPPA p.Ile183Val (c.547A>G) is very rare (popmax 0.00538%, afr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

What do computational predictors say about CRPPA p.Ile183Val (c.547A>G)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

CRPPA p.Ile183Val

Q: What condition is associated with CRPPA p.Ile183Val (c.547A>G)?

CRPPA p.Ile183Val (c.547A>G) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, autosomal recessive limb-girdle muscular dystrophy type 2U (ClinVar).

c.547A>G · rs1330602558 · VCV1680783

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00538%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -1.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 1.4, phastCons 0.24
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	18.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00538% African / African-American · 4/74,304 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000312% 5/1,601,446 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00538%	18,576
European (non-Finnish)	8.51e-05%	1,175,540

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.Ile183Val
Coding: c.547A>G
MANE Select: NM_001101426
dbSNP: rs1330602558
Type: single nucleotide variant
Location: chr7:16376229 (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 183: a β-strand

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2U

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

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
CRPPA c.1119+3A>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-ile183val (accessed [today's date]).

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