Is LRPPRC p.Leu720Phe (c.2160A>T) pathogenic?

LRPPRC p.Leu720Phe (c.2160A>T) is classified Uncertain significance in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: ambiguous (0.5009); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRPPRC p.Leu720Phe (c.2160A>T)?

LRPPRC p.Leu720Phe (c.2160A>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRPPRC p.Leu720Phe (c.2160A>T) in the general population?

LRPPRC p.Leu720Phe (c.2160A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRPPRC p.Leu720Phe (c.2160A>T)?

AlphaMissense predicts ambiguous (score 0.5009) — an in-silico prediction, not a clinical call.

LRPPRC p.Leu720Phe

c.2160A>T · rs2466565181 · VCV2231403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5009 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5009	ambiguous
REVEL	0.415	indeterminate
SaProt	LLR -9.63	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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.Leu720Phe
Coding: c.2160A>T
MANE Select: NM_133259
dbSNP: rs2466565181
Type: single nucleotide variant
Location: chr2:43946163 (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 720: the 'interaction with becn1 and aedes aegypti venom allergen-1' region

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 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
LRPPRC p.Ala997Thr Uncertain significance ★★ ⚠ same condition
LRPPRC p.Arg1109Cys 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-leu720phe (accessed [today's date]).

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