Is CRPPA p.Ala136Val (c.407C>T) pathogenic?

CRPPA p.Ala136Val (c.407C>T) is classified Benign in CRPPA (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0928); Low-frequency (popmax 4.47%, nfe); Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

How common is CRPPA p.Ala136Val (c.407C>T) in the general population?

CRPPA p.Ala136Val (c.407C>T) is low-frequency (popmax 4.47%, nfe) (gnomAD).

What do computational predictors say about CRPPA p.Ala136Val (c.407C>T)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

CRPPA p.Ala136Val

Q: What condition is associated with CRPPA p.Ala136Val (c.407C>T)?

CRPPA p.Ala136Val (c.407C>T) 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.407C>T · rs61734789 · VCV129287

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.47%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Congenital Muscular Dystrophy, alpha-dystroglycan related

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 3.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	18.32	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 4.47% European (non-Finnish) · 52,714/1,179,826 alleles

Filtering AF 4.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.42%

Overall 3.65% 58,920/1,613,930 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.92%	17
European (non-Finnish)grpmax	4.47%	22
Remaining individualsnot grpmax-eligible	3.28%	31
Finnishnot grpmax-eligible	2.44%	41
South Asian	1.26%	79
Admixed American	1.15%	87
African / African-American	0.742%	135
Ashkenazi Jewishnot grpmax-eligible	0.422%	237
Middle Eastern	0.313%	319
East Asian	0.00446%	22,438

Amish 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.Ala136Val
Coding: c.407C>T
MANE Select: NM_001101426
dbSNP: rs61734789
Type: single nucleotide variant
Location: chr7:16406188 (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 136: an α-helix

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.Ala136= 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.Arg205Cys Likely pathogenic ★★ same condition
CRPPA p.Arg268Ter Pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely 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-ala136val (accessed [today's date]).

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