Is LPP p.Arg452Ter (c.1354C>T) pathogenic?

LPP p.Arg452Ter (c.1354C>T) is classified Conflicting classifications of pathogenicity in LPP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-11-03). Very rare (popmax 0.00847%, nfe); Associated with acute myeloid leukemia.

What condition is associated with LPP p.Arg452Ter (c.1354C>T)?

LPP p.Arg452Ter (c.1354C>T) is associated with acute myeloid leukemia (ClinVar).

How common is LPP p.Arg452Ter (c.1354C>T) in the general population?

LPP p.Arg452Ter (c.1354C>T) is very rare (popmax 0.00847%, nfe) (gnomAD).

LPP p.Arg452Ter

c.1354C>T · rs202115941 · VCV1028399

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00847%, nfe)

Conditions

acute myeloid leukemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00847% European (non-Finnish) · 100/1,180,022 alleles

Filtering AF 0.00708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0066%

Overall 0.00638% 103/1,613,960 alleles · very rare exomes 93/1,461,870 · genomes 10/152,090 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00847%	11,800
African / African-American	0.00401%	24,960

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: LPP
Protein: p.Arg452Ter
Coding: c.1354C>T
MANE Select: NM_001375462
dbSNP: rs202115941
Type: single nucleotide variant
Location: chr3:188760226 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 452: the lim zinc-binding 1 domain

Full LPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LPP p.Arg140Trp Uncertain significance ★★ ⚠ same condition
LPP p.Ser151Pro Uncertain significance ★ ⚠ same condition
LPP c.1113+51T>C Benign ★★ same type
LPP c.1240+249G>A Benign ★★ same type
LPP c.1240+75A>G Benign ★★ same type
LPP c.1410+155C>T Benign ★★ same type
LPP c.1410+157T>C Benign ★★ same type
LPP c.1410+162G>A 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/lpp-p-arg452ter (accessed [today's date]).

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