Is LRP2 p.Ser2019= (c.6057A>G) pathogenic?

LRP2 p.Ser2019= (c.6057A>G) is classified Likely benign in LRP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-31). Rare (popmax 0.108%, afr); Associated with Donnai-Barrow syndrome.

What condition is associated with LRP2 p.Ser2019= (c.6057A>G)?

LRP2 p.Ser2019= (c.6057A>G) is associated with Donnai-Barrow syndrome (ClinVar).

How common is LRP2 p.Ser2019= (c.6057A>G) in the general population?

LRP2 p.Ser2019= (c.6057A>G) is rare (popmax 0.108%, afr) (gnomAD).

LRP2 p.Ser2019=

c.6057A>G · rs150970767 · VCV1559954

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

Conditions

Donnai-Barrow syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.55	GERP -0.11, phastCons 1
Overall
CADD	7.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% African / African-American · 81/75,050 alleles

Filtering AF 0.0889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.082%

Overall 0.00576% 93/1,614,084 alleles · rare exomes 51/1,461,724 · genomes 42/152,360 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	927
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00667%	15,000

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.Ser2019=
Coding: c.6057A>G
MANE Select: NM_004525
dbSNP: rs150970767
Type: single nucleotide variant
Location: chr2:169212191 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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 p.Ser2019Leu Uncertain significance ★ same residue
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

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-ser2019 (accessed [today's date]).

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