Is LRP1 p.Asp100= (c.300C>T) pathogenic?

LRP1 p.Asp100= (c.300C>T) is classified Conflicting classifications of pathogenicity in LRP1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-07-30). Common (popmax 17.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with keratosis pilaris atrophicans.

What condition is associated with LRP1 p.Asp100= (c.300C>T)?

LRP1 p.Asp100= (c.300C>T) is associated with keratosis pilaris atrophicans, keratosis pilaris, developmental dysplasia of the hip 3 (ClinVar).

LRP1 p.Asp100=

Q: How common is LRP1 p.Asp100= (c.300C>T) in the general population?

LRP1 p.Asp100= (c.300C>T) is common (popmax 17.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.300C>T · rs1799986 · VCV930178

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 17.6%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

keratosis pilaris atrophicans

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -4.2
Overall
CADD	4.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.6% Middle Eastern · 1,069/6,062 alleles

Filtering AF 16.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.4%

Overall 14.2% 228,541/1,613,992 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	22%	5
Middle Easterngrpmax	17.6%	6
Finnishnot grpmax-eligible	17.4%	6
South Asian	14.9%	7
European (non-Finnish)	14.9%	7
Remaining individualsnot grpmax-eligible	13.8%	7
Amishnot grpmax-eligible	10.4%	10
East Asian	8.04%	12
Admixed American	7.25%	14
African / African-American	5.65%	18

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp100=
Coding: c.300C>T
MANE Select: NM_173177 · reported on NM_002332
dbSNP: rs1799986
Type: single nucleotide variant
Location: chr12:57141483 (GRCh38)
Structure: AlphaFold pLDDT 88.37
Residue 100: the 'required for transcriptional repression' region; the 'interaction with nr1d1' region; the 'interaction with ncor1 and ncor2' region

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

Disease context

keratosis pilaris atrophicans — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: keratosis pilaris developmental dysplasia of the hip 3

Similar variants

LRP1 c.3793+25G>A Benign ★★ same condition
LRP1 c.6842-22C>G Benign ★★ same condition
LRP1 c.8702-5C>T Benign ★★ same condition
LRP1 c.8893-7C>T Benign ★★ same condition
LRP1 c.9282+11C>T Benign ★★ same condition
LRP1 p.Ala2426= Benign ★★ same condition
LRP1 p.Asp2975= Benign ★★ same condition
LRP1 p.Cys1182= Benign ★★ 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-asp100 (accessed [today's date]).

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