Is LRPPRC p.Ser296= (c.888C>T) pathogenic?

LRPPRC p.Ser296= (c.888C>T) is classified Likely benign in LRPPRC (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-16). Ultra-rare (popmax 0.028%, afr); Associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.

What condition is associated with LRPPRC p.Ser296= (c.888C>T)?

LRPPRC p.Ser296= (c.888C>T) is associated with congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Ser296= (c.888C>T) in the general population?

LRPPRC p.Ser296= (c.888C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

LRPPRC p.Ser296=

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.888C>T · rs762093225 · VCV1114610

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

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 -2.1	GERP -4.7
Overall
CADD	2.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/74,892 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00273% 44/1,613,354 alleles · ultra-rare exomes 29/1,461,418 · genomes 15/151,936 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,566
South Asian	0.0121%	8,277
Admixed American	0.00333%	29,987
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.000763%	131,070

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.Ser296=
Coding: c.888C>T
MANE Select: NM_133259
dbSNP: rs762093225
Type: single nucleotide variant
Location: chr2:43974735 (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 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-ser296 (accessed [today's date]).

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