Is CRPPA p.Ala430Val (c.1289C>T) pathogenic?

CRPPA p.Ala430Val (c.1289C>T) is classified Uncertain significance in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.1708); Absent from gnomAD v4.1.

How common is CRPPA p.Ala430Val (c.1289C>T) in the general population?

CRPPA p.Ala430Val (c.1289C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRPPA p.Ala430Val (c.1289C>T)?

AlphaMissense predicts likely benign (score 0.1708) — an in-silico prediction, not a clinical call.

CRPPA p.Ala430Val

c.1289C>T · VCV3497281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1708 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,559,452)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1708	likely benign
REVEL	0.431	indeterminate
SaProt	LLR -8.73	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 5.9	GERP 4.5, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	19.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,559,452). 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.Ala430Val
Coding: c.1289C>T
MANE Select: NM_001101426
Type: single nucleotide variant
Location: chr7:16091762 (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 430: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); a UniProt-annotated variant site (in mddgc7); an α-helix

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

Similar variants

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
CRPPA c.1026+5G>C Uncertain significance ★★ 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-ala430val (accessed [today's date]).

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