Is LRPPRC p.Cys413fs (c.1216_1237dup) pathogenic?

LRPPRC p.Cys413fs (c.12161237dup) is classified Likely pathogenic in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-21). No gnomAD frequency available for this variant; Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Cys413fs (c.1216_1237dup)?

LRPPRC p.Cys413fs (c.1216_1237dup) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Cys413fs (c.1216_1237dup) in the general population?

LRPPRC p.Cys413fs (c.1216_1237dup) is no gnomAD frequency available for this variant (gnomAD).

LRPPRC p.Cys413fs

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.1216_1237dup · rs2466660937 · VCV2676324

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 10 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.44, phastCons 1

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.Cys413fs
Coding: c.1216_1237dup
MANE Select: NM_133259
dbSNP: rs2466660937
Type: Duplication
Location: chr2:43973818 (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 413: an α-helix

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.Cys413Phe Uncertain significance ⚠ same residue
LRPPRC p.Cys413Tyr Uncertain significance ⚠ same residue
LRPPRC p.Asn1190fs Likely pathogenic ★★ same condition
LRPPRC p.Gly1050fs Pathogenic ★★ same condition
LRPPRC p.His791fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Leu1259fs Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Lys1338Ter Pathogenic/Likely pathogenic ★★ same condition
LRPPRC p.Phe1222fs Pathogenic/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-cys413fs (accessed [today's date]).

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