Is LRPPRC p.Cys113Phe (c.338G>T) pathogenic?

LRPPRC p.Cys113Phe (c.338G>T) is classified Uncertain significance in LRPPRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely benign (0.2144); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRPPRC p.Cys113Phe (c.338G>T)?

LRPPRC p.Cys113Phe (c.338G>T) is associated with Inborn genetic diseases, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ClinVar).

How common is LRPPRC p.Cys113Phe (c.338G>T) in the general population?

LRPPRC p.Cys113Phe (c.338G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRPPRC p.Cys113Phe (c.338G>T)?

AlphaMissense predicts likely benign (score 0.2144) — an in-silico prediction, not a clinical call.

LRPPRC p.Cys113Phe

c.338G>T · rs750132738 · VCV1033050

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2144 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,940)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2144	likely benign
REVEL	0.431	indeterminate
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,567,940). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRPPRC
Protein: p.Cys113Phe
Coding: c.338G>T
MANE Select: NM_133259
dbSNP: rs750132738
Type: single nucleotide variant
Location: chr2:43982246 (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 113: an α-helix

Full LRPPRC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

Similar variants

LRPPRC p.Cys113= 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
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-cys113phe (accessed [today's date]).

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