Is LRP5 p.Asp213= (c.639C>T) pathogenic?

LRP5 p.Asp213= (c.639C>T) is classified Conflicting classifications of pathogenicity in LRP5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0401%, eas).

How common is LRP5 p.Asp213= (c.639C>T) in the general population?

LRP5 p.Asp213= (c.639C>T) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

LRP5 p.Asp213=

c.639C>T · rs150859573 · VCV196340

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

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 -14	GERP -3.9
Overall
CADD	0.321	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,868 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0322%

Overall 0.0307% 495/1,613,988 alleles · ultra-rare exomes 462/1,461,636 · genomes 33/152,352 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
East Asiangrpmax	0.0401%	2,493
European (non-Finnish)	0.0363%	2,757
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.015%	6,667
South Asian	0.00989%	10,115
African / African-American	0.00799%	12,510
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
Finnishnot grpmax-eligible	0.00156%	64,008

Amish 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: LRP5
Protein: p.Asp213=
Coding: c.639C>T
MANE Select: NM_002335
dbSNP: rs150859573
Type: single nucleotide variant
Location: chr11:68357800 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 213: the 'beta-propeller 1' region

Full LRP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRP5 c.1412+1G>A Pathogenic ★★ same type
LRP5 c.2827+1G>A Pathogenic ★★ same type
LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same type
LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same type
LRP5 c.884-2A>G Likely pathogenic ★★ same type
LRP5 p.Ala214Thr Pathogenic ★★ same type
LRP5 p.Ala242Thr Pathogenic/Likely pathogenic ★★ same type
LRP5 p.Ala422Ser Likely pathogenic ★★ ⚠ 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/lrp5-p-asp213 (accessed [today's date]).

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