Is LRPPRC p.Pro41Arg (c.122C>G) pathogenic?

LRPPRC p.Pro41Arg (c.122C>G) is classified Uncertain significance in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.09); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRPPRC p.Pro41Arg (c.122C>G)?

LRPPRC p.Pro41Arg (c.122C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LRPPRC p.Pro41Arg (c.122C>G) in the general population?

LRPPRC p.Pro41Arg (c.122C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRPPRC p.Pro41Arg (c.122C>G)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

LRPPRC p.Pro41Arg

c.122C>G · VCV4100027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.095, phastCons 0.24
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	9.901	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRPPRC
Protein: p.Pro41Arg
Coding: c.122C>G
MANE Select: NM_133259
Type: single nucleotide variant
Location: chr2:43995826 (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

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

Similar variants

LRPPRC p.Pro41Ser Uncertain significance ★ ⚠ same residue
LRPPRC p.Pro41= Likely benign ★ same residue
LRPPRC c.1369+5G>A Uncertain significance ★★ same condition
LRPPRC p.Ala1093Thr Uncertain significance ★★ ⚠ same condition
LRPPRC p.Ala1360Ser Uncertain significance ★★ ⚠ same condition
LRPPRC p.Ala37Ser Uncertain significance ★★ ⚠ same condition
LRPPRC p.Ala417Thr Uncertain significance ★★ ⚠ same condition
LRPPRC p.Ala516Val Uncertain significance ★★ ⚠ 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-pro41arg (accessed [today's date]).

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