Is LDLR p.Asp433Val (c.1298A>T) pathogenic?

LDLR p.Asp433Val (c.1298A>T) is classified Likely pathogenic in LDLR (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9606); Absent from gnomAD v4.1; Associated with Abnormal circulating lipid concentration.

What condition is associated with LDLR p.Asp433Val (c.1298A>T)?

LDLR p.Asp433Val (c.1298A>T) is associated with Abnormal circulating lipid concentration (ClinVar).

How common is LDLR p.Asp433Val (c.1298A>T) in the general population?

LDLR p.Asp433Val (c.1298A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LDLR p.Asp433Val (c.1298A>T)?

AlphaMissense predicts likely pathogenic (score 0.9606) — an in-silico prediction, not a clinical call.

LDLR p.Asp433Val

c.1298A>T · rs2516004016 · VCV1705273

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9606 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Abnormal circulating lipid concentration

Computational evidence

Protein change
AlphaMissense	0.9606	likely pathogenic ✓ concordant with ClinVar
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -11.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 42 kb · p 0.91 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LDLR
Protein: p.Asp433Val
Coding: c.1298A>T
MANE Select: NM_000527
dbSNP: rs2516004016
Type: single nucleotide variant
Location: chr19:11113389 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 433: a UniProt-annotated variant site (in fhcl1; osaka-3); a β-strand

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

Disease context

Abnormal circulating lipid concentration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLR p.Asp433His Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp433Ala Likely pathogenic ★ ⚠ same residue
LDLR p.Asp433Asn Likely pathogenic ★ same residue
LDLR p.Asp433Tyr Likely pathogenic ★ same residue
LDLR p.Asp433_Thr434del Likely pathogenic ★ same residue
LDLR p.Asp433del Likely pathogenic ★ same residue
LDLR p.Ser447fs Pathogenic same condition
LDLR c.1186+5G>A Likely pathogenic ★★★ same type

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/ldlr-p-asp433val (accessed [today's date]).

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