Is LRPPRC p.Pro47Thr (c.139C>A) pathogenic?

LRPPRC p.Pro47Thr (c.139C>A) is classified Uncertain significance in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-29). AlphaMissense: likely benign (0.0874); No allele count reported in gnomAD v4.1 (AN 1,404,700); Associated with Inborn genetic diseases.

What condition is associated with LRPPRC p.Pro47Thr (c.139C>A)?

LRPPRC p.Pro47Thr (c.139C>A) is associated with Inborn genetic diseases (ClinVar).

How common is LRPPRC p.Pro47Thr (c.139C>A) in the general population?

LRPPRC p.Pro47Thr (c.139C>A) is no allele count reported in gnomAD v4.1 (AN 1,404,700) (gnomAD).

What do computational predictors say about LRPPRC p.Pro47Thr (c.139C>A)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

LRPPRC p.Pro47Thr

c.139C>A · rs1411378241 · VCV2262404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,404,700)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.54	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 4.5	GERP 0.17, phastCons 0.96
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	19.91	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 1,404,700). 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.Pro47Thr
Coding: c.139C>A
MANE Select: NM_133259
dbSNP: rs1411378241
Type: single nucleotide variant
Location: chr2:43995809 (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.Pro47Arg Uncertain significance ★★ ⚠ same residue
LRPPRC p.Pro47= 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-pro47thr (accessed [today's date]).

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