Is LRPPRC p.Gln82= (c.246G>A) pathogenic?

LRPPRC p.Gln82= (c.246G>A) is classified Benign in LRPPRC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 73.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Gln82= (c.246G>A)?

LRPPRC p.Gln82= (c.246G>A) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

LRPPRC p.Gln82=

Q: How common is LRPPRC p.Gln82= (c.246G>A) in the general population?

LRPPRC p.Gln82= (c.246G>A) is common (popmax 73.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.246G>A · rs6741066 · VCV129548

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 73.6%, nfe) — too common for a highly-penetrant pathogenic allele

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -4.7
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 73.6% European (non-Finnish) · 867,489/1,179,070 alleles

Filtering AF 73.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 73.4%

Overall 69.3% 1,118,407/1,612,704 alleles · common exomes 1,015,292/1,460,614 · genomes 103,115/152,090 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	73.9%	1
European (non-Finnish)grpmax	73.6%	1
Finnishnot grpmax-eligible	73.5%	1
Middle Eastern	71.9%	1
African / African-American	70.4%	1
Remaining individualsnot grpmax-eligible	67.8%	1
Amishnot grpmax-eligible	60%	2
South Asian	53.6%	2
Admixed American	51.4%	2
East Asian	5.59%	18

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln82=
Coding: c.246G>A
MANE Select: NM_133259
dbSNP: rs6741066
Type: single nucleotide variant
Location: chr2:43982338 (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 82: 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.Gln82Ter Pathogenic/Likely pathogenic ★★ same residue
LRPPRC p.Gln82fs Likely pathogenic ★ same residue
LRPPRC p.Gln82Pro Uncertain significance ★ ⚠ same residue
LRPPRC p.Gln82His Likely benign ★ same residue
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

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-gln82 (accessed [today's date]).

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