Is LRPPRC p.Ala16fs (c.46dup) pathogenic?

LRPPRC p.Ala16fs (c.46dup) is classified Pathogenic in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-14). No allele count reported in gnomAD v4.1 (AN 1,511,264).

How common is LRPPRC p.Ala16fs (c.46dup) in the general population?

LRPPRC p.Ala16fs (c.46dup) is no allele count reported in gnomAD v4.1 (AN 1,511,264) (gnomAD).

LRPPRC p.Ala16fs

c.46dup · rs2465901202 · VCV2016441

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,511,264)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.64	GERP -4.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,511,264). 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.Ala16fs
Coding: c.46dup
MANE Select: NM_133259
dbSNP: rs2465901202
Type: Duplication
Location: chr2:43995901 (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.Ala16= Likely benign ★ same residue
LRPPRC p.Asn1190fs Likely pathogenic ★★ same type
LRPPRC p.Gly1050fs Pathogenic ★★ same type
LRPPRC p.His791fs Pathogenic/Likely pathogenic ★★ same type
LRPPRC p.Leu1259fs Pathogenic/Likely pathogenic ★★ same type
LRPPRC p.Lys1338Ter Pathogenic/Likely pathogenic ★★ same type
LRPPRC p.Phe1222fs Pathogenic/Likely pathogenic ★★ same type
LRPPRC c.1156-13dup Benign/Likely benign ★★ 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-ala16fs (accessed [today's date]).

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