Is CRPPA p.Ser107Ile (c.320G>T) pathogenic?

CRPPA p.Ser107Ile (c.320G>T) is classified Conflicting classifications of pathogenicity in CRPPA (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1142); Ultra-rare (popmax 0.0297%, nfe); Associated with Congenital Muscular Dystrophy, alpha-dystroglycan related.

How common is CRPPA p.Ser107Ile (c.320G>T) in the general population?

CRPPA p.Ser107Ile (c.320G>T) is ultra-rare (popmax 0.0297%, nfe) (gnomAD).

What do computational predictors say about CRPPA p.Ser107Ile (c.320G>T)?

AlphaMissense predicts likely benign (score 0.1142) — an in-silico prediction, not a clinical call.

CRPPA p.Ser107Ile

Q: What condition is associated with CRPPA p.Ser107Ile (c.320G>T)?

CRPPA p.Ser107Ile (c.320G>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.320G>T · rs199691459 · VCV285066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1142 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0297%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Congenital Muscular Dystrophy, alpha-dystroglycan related

Computational evidence

Protein change
AlphaMissense	0.1142	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -9.80	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 -2.4	GERP -0.77
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	14.26	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 0.0297% European (non-Finnish) · 350/1,179,832 alleles

Filtering AF 0.0271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0261%

Overall 0.0239% 385/1,613,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,850
European (non-Finnish)grpmax	0.0297%	3,371
Remaining individualsnot grpmax-eligible	0.0208%	4,804
Finnishnot grpmax-eligible	0.00625%	16,002
African / African-American	0.00267%	37,455

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.Ser107Ile
Coding: c.320G>T
MANE Select: NM_001101426
dbSNP: rs199691459
Type: single nucleotide variant
Location: chr7:16406275 (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 107: 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 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
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-ser107ile (accessed [today's date]).

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