Is LRP4 p.Phe1635= (c.4905C>T) pathogenic?

LRP4 p.Phe1635= (c.4905C>T) is classified Benign in LRP4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 61.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cenani-Lenz syndactyly syndrome.

What condition is associated with LRP4 p.Phe1635= (c.4905C>T)?

LRP4 p.Phe1635= (c.4905C>T) is associated with Cenani-Lenz syndactyly syndrome, sclerosteosis 2, congenital myasthenic syndrome 17 (ClinVar).

LRP4 p.Phe1635=

Q: How common is LRP4 p.Phe1635= (c.4905C>T) in the general population?

LRP4 p.Phe1635= (c.4905C>T) is common (popmax 61.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4905C>T · rs2290883 · VCV304853

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 61.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Cenani-Lenz syndactyly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.81	GERP -3.7
Overall
CADD	6.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.6% East Asian · 27,643/44,864 alleles

Filtering AF 61% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.8%

Overall 15.5% 250,501/1,613,984 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	61.6%	2
Admixed American	34.1%	3
Finnishnot grpmax-eligible	23.3%	4
South Asian	20.1%	5
Remaining individualsnot grpmax-eligible	14.8%	7
European (non-Finnish)	13.2%	8
Middle Eastern	10.7%	9
Amishnot grpmax-eligible	8.11%	12
Ashkenazi Jewishnot grpmax-eligible	5.89%	17
African / African-American	2.65%	38

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: LRP4
Protein: p.Phe1635=
Coding: c.4905C>T
dbSNP: rs2290883
Type: single nucleotide variant
Location: chr11:46868646 (GRCh38)

Full LRP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cenani-Lenz syndactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sclerosteosis 2 congenital myasthenic syndrome 17

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/lrp4-p-phe1635 (accessed [today's date]).

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