Is LRPPRC p.Pro827= (c.2481A>G) pathogenic?

LRPPRC p.Pro827= (c.2481A>G) is classified Benign in LRPPRC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.2%, nfe); Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Pro827= (c.2481A>G)?

LRPPRC p.Pro827= (c.2481A>G) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Pro827= (c.2481A>G) in the general population?

LRPPRC p.Pro827= (c.2481A>G) is low-frequency (popmax 1.2%, nfe) (gnomAD).

LRPPRC p.Pro827=

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.2481A>G · rs115993634 · VCV138146

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, nfe)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -5.9
Overall
CADD	4.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.2% European (non-Finnish) · 14,162/1,179,200 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.994% 16,030/1,613,194 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.2%	83
Remaining individualsnot grpmax-eligible	0.754%	133
Admixed American	0.535%	187
South Asian	0.513%	195
Ashkenazi Jewishnot grpmax-eligible	0.51%	196
Finnishnot grpmax-eligible	0.481%	208
African / African-American	0.185%	540
Middle Eastern	0.181%	551

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: LRPPRC
Protein: p.Pro827=
Coding: c.2481A>G
MANE Select: NM_133259
dbSNP: rs115993634
Type: single nucleotide variant
Location: chr2:43943710 (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 827: 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 c.1369+1G>C Likely pathogenic ★★ same condition
LRPPRC c.1582+7A>G Likely pathogenic ★★ same condition
LRPPRC c.1677+1G>A Likely pathogenic ★★ same condition
LRPPRC c.1677+1G>T Likely pathogenic ★★ same condition
LRPPRC c.1678-1G>A Likely pathogenic ★★ same condition
LRPPRC c.1735+2T>C Likely pathogenic ★★ same condition
LRPPRC c.1965+2T>C Likely pathogenic ★★ same condition
LRPPRC c.2505-2A>T 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-pro827 (accessed [today's date]).

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