Is LRP4 p.Ser900Phe (c.2699C>T) pathogenic?

LRP4 p.Ser900Phe (c.2699C>T) is classified Uncertain significance in LRP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.4985); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with LRP4 p.Ser900Phe (c.2699C>T)?

LRP4 p.Ser900Phe (c.2699C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRP4 p.Ser900Phe (c.2699C>T) in the general population?

LRP4 p.Ser900Phe (c.2699C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LRP4 p.Ser900Phe (c.2699C>T)?

AlphaMissense predicts ambiguous (score 0.4985) — an in-silico prediction, not a clinical call.

LRP4 p.Ser900Phe

c.2699C>T · VCV4048750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4985	ambiguous
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -10.28	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Overall 0.000124% 2/1,614,106 alleles · very rare exomes 1/1,461,864 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
African / African-American	0.00133%	74,942

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.Ser900Phe
Coding: c.2699C>T
MANE Select: NM_002334
Type: single nucleotide variant
Location: chr11:46881817 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRP4 p.Ala1661Thr Uncertain significance ★★ ⚠ same condition
LRP4 p.Ala1727Thr Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1194Trp Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1425Gln Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg1506Trp Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg202His Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg232Cys Uncertain significance ★★ ⚠ same condition
LRP4 p.Arg249His Uncertain significance ★★ ⚠ 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/lrp4-p-ser900phe (accessed [today's date]).

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