Is LRPPRC p.Gln356= (c.1068A>G) pathogenic?

LRPPRC p.Gln356= (c.1068A>G) is classified Benign in LRPPRC (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 49.7%, eas) — 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.Gln356= (c.1068A>G)?

LRPPRC p.Gln356= (c.1068A>G) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

LRPPRC p.Gln356=

Q: How common is LRPPRC p.Gln356= (c.1068A>G) in the general population?

LRPPRC p.Gln356= (c.1068A>G) is common (popmax 49.7%, eas) — 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.1068A>G · rs4953042 · VCV129547

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 49.7%, eas) — 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -4.7, phastCons 0.95
Overall
CADD	1.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.7% East Asian · 22,261/44,822 alleles

Filtering AF 49.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.9%

Overall 17.3% 278,294/1,610,560 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	49.7%	2
South Asian	32%	3
Admixed American	28.3%	4
Amishnot grpmax-eligible	19.3%	5
Remaining individualsnot grpmax-eligible	18.1%	6
Finnishnot grpmax-eligible	17.7%	6
Ashkenazi Jewishnot grpmax-eligible	15.6%	6
European (non-Finnish)	15.1%	7
Middle Eastern	14.3%	7
African / African-American	4.69%	21

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.Gln356=
Coding: c.1068A>G
MANE Select: NM_133259
dbSNP: rs4953042
Type: single nucleotide variant
Location: chr2:43974237 (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 356: 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 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-gln356 (accessed [today's date]).

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