Is LRP2 p.Ser803= (c.2409T>G) pathogenic?

LRP2 p.Ser803= (c.2409T>G) is classified Conflicting classifications of pathogenicity in LRP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-05-06). Very rare (popmax 0.00305%, nfe); Associated with Donnai-Barrow syndrome.

What condition is associated with LRP2 p.Ser803= (c.2409T>G)?

LRP2 p.Ser803= (c.2409T>G) is associated with Donnai-Barrow syndrome (ClinVar).

How common is LRP2 p.Ser803= (c.2409T>G) in the general population?

LRP2 p.Ser803= (c.2409T>G) is very rare (popmax 0.00305%, nfe) (gnomAD).

LRP2 p.Ser803=

c.2409T>G · rs544785940 · VCV893656

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Conditions

Donnai-Barrow syndrome

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 0.51	GERP -2.1, phastCons 0.02
Overall
CADD	8.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,179,546 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00236% 38/1,613,266 alleles · very rare exomes 35/1,461,208 · genomes 3/152,058 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00305%	32,765
Remaining individualsnot grpmax-eligible	0.0016%	62,458
African / African-American	0.00134%	74,878

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: LRP2
Protein: p.Ser803=
Coding: c.2409T>G
MANE Select: NM_004525
dbSNP: rs544785940
Type: single nucleotide variant
Location: chr2:169259129 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 803: a turn

Full LRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Donnai-Barrow syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRP2 c.12019+1G>A Likely pathogenic ★★ same condition
LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same condition
LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same condition
LRP2 c.8452+1G>A Pathogenic ★★ same condition
LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg2225Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg278Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg3184Ter Pathogenic/Likely 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/lrp2-p-ser803 (accessed [today's date]).

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