Is LRP1 p.Ser428= (c.1284G>A) pathogenic?

LRP1 p.Ser428= (c.1284G>A) is classified Uncertain significance in LRP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). Very rare (popmax 0.00446%, eas); Associated with developmental dysplasia of the hip 3.

What condition is associated with LRP1 p.Ser428= (c.1284G>A)?

LRP1 p.Ser428= (c.1284G>A) is associated with developmental dysplasia of the hip 3, keratosis pilaris atrophicans (ClinVar).

How common is LRP1 p.Ser428= (c.1284G>A) in the general population?

LRP1 p.Ser428= (c.1284G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

LRP1 p.Ser428=

c.1284G>A · VCV3575004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

developmental dysplasia of the hip 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1	GERP -4.4
Overall
CADD	17.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,848 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00279% 45/1,613,846 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,424
European (non-Finnish)	0.00331%	30,256
South Asian	0.0022%	45,536
Admixed American	0.00167%	59,970
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: LRP1
Protein: p.Ser428=
Coding: c.1284G>A
MANE Select: NM_173177 · reported on NM_002332
Type: single nucleotide variant
Location: chr12:57156150 (GRCh38)
Structure: AlphaFold pLDDT 88.37

Full LRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental dysplasia of the hip 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: keratosis pilaris atrophicans

Similar variants

LRP1 p.Asp100= Conflicting classifications of pathogenicity ★ same condition
LRP1 p.Asp2632Glu Uncertain significance ★ ⚠ same condition
LRP1 p.Gly169Asp Uncertain significance ★ ⚠ same condition
LRP1 p.His3000Arg Uncertain significance ★ same condition
LRP1 p.His3282Arg Uncertain significance ★ ⚠ same condition
LRP1 p.Ile405Thr Uncertain significance ★ ⚠ same condition
LRP1 c.2798-4C>A Pathogenic same condition
LRP1 p.Arg1783Trp Pathogenic ⚠ 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/lrp1-p-ser428 (accessed [today's date]).

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