Is CRPPA p.Ser19Arg (c.55A>C) pathogenic?

CRPPA p.Ser19Arg (c.55A>C) is classified Benign in CRPPA (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0949); Common (popmax 34.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

What do computational predictors say about CRPPA p.Ser19Arg (c.55A>C)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

CRPPA p.Ser19Arg

Q: What condition is associated with CRPPA p.Ser19Arg (c.55A>C)?

CRPPA p.Ser19Arg (c.55A>C) 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).

Q: How common is CRPPA p.Ser19Arg (c.55A>C) in the general population?

CRPPA p.Ser19Arg (c.55A>C) is common (popmax 34.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.55A>C · rs7782939 · VCV129288

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 34.3%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Congenital Muscular Dystrophy, alpha-dystroglycan related

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.18	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 -0.054	GERP -1.7
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	3.384	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

Grpmax group 34.3% South Asian · 13,226/38,600 alleles

Filtering AF 33.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.6%

Overall 30.4% 394,087/1,297,340 alleles · common exomes 348,776/1,145,802 · genomes 45,311/151,538 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	34.3%	3
Amishnot grpmax-eligible	31.3%	3
European (non-Finnish)	30.6%	3
Remaining individualsnot grpmax-eligible	30.4%	3
Finnishnot grpmax-eligible	29.4%	3
African / African-American	29.4%	3
Admixed American	28.5%	4
East Asian	27.1%	4
Middle Eastern	25.7%	4
Ashkenazi Jewishnot grpmax-eligible	24.3%	4

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.Ser19Arg
Coding: c.55A>C
MANE Select: NM_001101426
dbSNP: rs7782939
Type: single nucleotide variant
Location: chr7:16421268 (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 19: the 'disordered' region

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.Ser19fs Pathogenic ★★ same residue
CRPPA p.Ser19Glufs Pathogenic/Likely pathogenic ★★ 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-ser19arg (accessed [today's date]).

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