Is LRP2 p.Phe3049= (c.9147C>T) pathogenic?

LRP2 p.Phe3049= (c.9147C>T) is classified Benign/Likely benign in LRP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-29). Rare (popmax 0.481%, afr); Associated with Donnai-Barrow syndrome.

What condition is associated with LRP2 p.Phe3049= (c.9147C>T)?

LRP2 p.Phe3049= (c.9147C>T) is associated with Donnai-Barrow syndrome (ClinVar).

How common is LRP2 p.Phe3049= (c.9147C>T) in the general population?

LRP2 p.Phe3049= (c.9147C>T) is rare (popmax 0.481%, afr) (gnomAD).

LRP2 p.Phe3049=

c.9147C>T · rs146115458 · VCV720292

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.481%, afr)

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 -5.2	GERP -4.8
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.481% African / African-American · 361/75,002 alleles

Filtering AF 0.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.424%

Overall 0.0288% 465/1,614,070 alleles · rare exomes 242/1,461,866 · genomes 223/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.481%	208
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0667%	1,500
East Asian	0.00668%	14,962
South Asian	0.0022%	45,533
European (non-Finnish)	0.0011%	90,770

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.Phe3049=
Coding: c.9147C>T
MANE Select: NM_004525
dbSNP: rs146115458
Type: single nucleotide variant
Location: chr2:169188151 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3049: the ldl-receptor class a 24 domain; a β-strand

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-phe3049 (accessed [today's date]).

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