Is LRPPRC p.Arg575Ter (c.1723C>T) pathogenic?

LRPPRC p.Arg575Ter (c.1723C>T) is classified Pathogenic/Likely pathogenic in LRPPRC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-17). Very rare (popmax 0.00167%, amr); Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Arg575Ter (c.1723C>T)?

LRPPRC p.Arg575Ter (c.1723C>T) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Arg575Ter (c.1723C>T) in the general population?

LRPPRC p.Arg575Ter (c.1723C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

LRPPRC p.Arg575Ter

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.1723C>T · rs774934005 · VCV554351

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 38
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1	GERP -1.7, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,994 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,470 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
South Asian	0.0011%	91,030
European (non-Finnish)	0.000254%	393,289

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.Arg575Ter
Coding: c.1723C>T
MANE Select: NM_133259
dbSNP: rs774934005
Type: single nucleotide variant
Location: chr2:43949614 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.35 · 2 PDB

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.Arg575= Uncertain significance 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
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

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-arg575ter (accessed [today's date]).

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