Is LRPPRC p.Arg857fs (c.2569_2585del) pathogenic?

LRPPRC p.Arg857fs (c.25692585del) is classified Likely pathogenic in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). No gnomAD frequency available for this variant; Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Arg857fs (c.2569_2585del)?

LRPPRC p.Arg857fs (c.2569_2585del) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Arg857fs (c.2569_2585del) in the general population?

LRPPRC p.Arg857fs (c.2569_2585del) is no gnomAD frequency available for this variant (gnomAD).

LRPPRC p.Arg857fs

Q: How is Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2569_2585del · rs2466525468 · VCV2676319

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.008	GERP -5.9, phastCons 0.92

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: LRPPRC
Protein: p.Arg857fs
Coding: c.2569_2585del
MANE Select: NM_133259
dbSNP: rs2466525468
Type: Deletion
Location: chr2:43934798 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.35 · 2 PDB
Residue 857: the 'interaction with becn1 and aedes aegypti venom allergen-1' region

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

Disease context

congenital lactic acidosis, Saguenay-Lac-Saint-Jean type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

LRPPRC p.Arg857Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
LRPPRC c.1730_1735+1del Likely pathogenic ★★ same condition
LRPPRC c.3710-1del Likely pathogenic ★★ same condition
LRPPRC p.Ala1051fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Ala42fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Asn1246fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Asn454fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Gln1005fs 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/lrpprc-p-arg857fs (accessed [today's date]).

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