Is CRPPA p.Ser385= (c.1155T>C) pathogenic?

CRPPA p.Ser385= (c.1155T>C) is classified Likely benign in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). Very rare (popmax 0.00172%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2U.

What condition is associated with CRPPA p.Ser385= (c.1155T>C)?

CRPPA p.Ser385= (c.1155T>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.Ser385= (c.1155T>C) in the general population?

CRPPA p.Ser385= (c.1155T>C) is very rare (popmax 0.00172%, amr) (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.

CRPPA p.Ser385=

c.1155T>C · rs754598412 · VCV2027858

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2U

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 1.7	GERP 4, phastCons 0.75
Overall
CADD	3.208	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/58,260 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000819% 13/1,587,174 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0309%	3,232
Admixed Americangrpmax	0.00172%	58,260
Remaining individualsnot grpmax-eligible	0.00162%	61,556
European (non-Finnish)	0.000172%	580,289

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.Ser385=
Coding: c.1155T>C
MANE Select: NM_001101426
dbSNP: rs754598412
Type: single nucleotide variant
Location: chr7:16216162 (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 385: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); an α-helix

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 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-ser385 (accessed [today's date]).

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