Is CRPPA p.Lys263= (c.789G>A) pathogenic?

CRPPA p.Lys263= (c.789G>A) is classified Likely pathogenic in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). Absent from gnomAD v4.1; Associated with CRPPA-related disorder.

What condition is associated with CRPPA p.Lys263= (c.789G>A)?

CRPPA p.Lys263= (c.789G>A) is associated with CRPPA-related disorder (ClinVar).

How common is CRPPA p.Lys263= (c.789G>A) in the general population?

CRPPA p.Lys263= (c.789G>A) is absent from gnomAD v4.1 (gnomAD).

CRPPA p.Lys263=

c.789G>A · rs776803163 · VCV2572373

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,565,874)

Conditions

CRPPA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.81	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.60	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 3.8, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,565,874). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRPPA
Protein: p.Lys263=
Coding: c.789G>A
MANE Select: NM_001101426
dbSNP: rs776803163
Type: single nucleotide variant
Location: chr7:16308523 (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 263: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); a functional site (positions substrate for the nucleophilic attack)

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

Disease context

CRPPA-related disorder

Similar variants

CRPPA p.Arg205Cys Likely pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.1251+4G>A Uncertain significance ★★ same condition
CRPPA c.*2235A>C Uncertain significance ★★ same condition
CRPPA c.*2237A>G Uncertain significance ★★ same condition
CRPPA c.*2248C>T Uncertain significance ★★ same condition
CRPPA c.*2263A>C Uncertain significance ★★ same condition
CRPPA c.*2265A>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-lys263 (accessed [today's date]).

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