Is CRPPA p.Pro384Leu (c.1151C>T) pathogenic?

CRPPA p.Pro384Leu (c.1151C>T) is classified Conflicting classifications of pathogenicity in CRPPA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0689); Very rare (popmax 0.00135%, afr).

How common is CRPPA p.Pro384Leu (c.1151C>T) in the general population?

CRPPA p.Pro384Leu (c.1151C>T) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about CRPPA p.Pro384Leu (c.1151C>T)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

CRPPA p.Pro384Leu

c.1151C>T · rs752622525 · VCV199058

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -8.05	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 2.9	GERP 0.2, phastCons 0.94
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	5.215	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 0.00135% African / African-American · 1/73,900 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000378% 6/1,586,008 alleles · very rare exomes 3/1,433,996 · genomes 3/152,012 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,900
European (non-Finnish)	0.000431%	232,005

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.Pro384Leu
Coding: c.1151C>T
MANE Select: NM_001101426
dbSNP: rs752622525
Type: single nucleotide variant
Location: chr7:16216166 (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 384: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy)

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

Similar variants

CRPPA p.Pro384= Likely benign ★ same residue
CRPPA c.1120-1G>T Pathogenic ★★ same type
CRPPA c.258-1G>C Pathogenic/Likely pathogenic ★★ same type
CRPPA c.835+2T>C Pathogenic/Likely pathogenic ★★ same type
CRPPA p.Arg184Ter Pathogenic ★★ same type
CRPPA p.Arg205Cys Likely pathogenic ★★ same type
CRPPA p.Arg268Ter Pathogenic ★★ same type
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same type

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-pro384leu (accessed [today's date]).

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