Is LRPPRC p.Ala17Val (c.50C>T) pathogenic?

LRPPRC p.Ala17Val (c.50C>T) is classified Uncertain significance in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1232); Ultra-rare (popmax 0.0267%, amr).

How common is LRPPRC p.Ala17Val (c.50C>T) in the general population?

LRPPRC p.Ala17Val (c.50C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about LRPPRC p.Ala17Val (c.50C>T)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

LRPPRC p.Ala17Val

c.50C>T · rs896539791 · VCV2141777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.67	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 3.4	GERP -0.79, phastCons 0.53
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	15.14	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

Grpmax group 0.0267% Admixed American · 13/48,648 alleles

Filtering AF 0.0157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00251% 38/1,512,248 alleles · ultra-rare exomes 27/1,359,946 · genomes 11/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,742
Middle Eastern	0.0226%	4,428
African / African-American	0.0214%	4,662
Remaining individualsnot grpmax-eligible	0.0068%	14,697
European (non-Finnish)	0.000439%	227,598

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.Ala17Val
Coding: c.50C>T
MANE Select: NM_133259
dbSNP: rs896539791
Type: single nucleotide variant
Location: chr2:43995898 (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

Similar variants

LRPPRC p.Ala17= Likely benign ★ same residue
LRPPRC p.Ala17Thr Likely benign ★ same residue
LRPPRC c.1369+1G>C Likely pathogenic ★★ same type
LRPPRC c.1582+7A>G Likely pathogenic ★★ same type
LRPPRC c.1677+1G>A Likely pathogenic ★★ same type
LRPPRC c.1677+1G>T Likely pathogenic ★★ same type
LRPPRC c.1678-1G>A Likely pathogenic ★★ same type
LRPPRC c.1735+2T>C Likely pathogenic ★★ same type

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-ala17val (accessed [today's date]).

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