Is LDLR p.Val800Ile (c.2398G>A) pathogenic?

LDLR p.Val800Ile (c.2398G>A) is classified Benign/Likely benign in LDLR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-23). AlphaMissense: likely benign (0.0776); Ultra-rare (popmax 0.0417%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Val800Ile (c.2398G>A)?

LDLR p.Val800Ile (c.2398G>A) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Val800Ile (c.2398G>A) in the general population?

LDLR p.Val800Ile (c.2398G>A) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about LDLR p.Val800Ile (c.2398G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

LDLR p.Val800Ile

c.2398G>A · rs200243555 · VCV183135

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.97	GERP -2.3
Regional constraint	o/e 1.00	unconstrained · MANE · 42 kb · p 0.91 · regional, not allelic
Overall
CADD	0.506	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 0.0417% Admixed American · 25/59,976 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00316% 51/1,613,614 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,399
South Asian	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00157%	63,688
European (non-Finnish)	0.00136%	73,748
African / African-American	0.00133%	74,916

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: LDLR
Protein: p.Val800Ile
Coding: c.2398G>A
MANE Select: NM_000527
dbSNP: rs200243555
Type: single nucleotide variant
Location: chr19:11129521 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 800: a UniProt-annotated variant site (in fhcl1)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia hypercholesterolemia, familial, 1

Similar variants

LDLR p.Val800Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Val800Leu Uncertain significance ⚠ same residue
LDLR p.Val800fs Likely pathogenic ★★★ same residue
LDLR p.Val800_Leu802del Conflicting classifications of pathogenicity ★ same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>A Pathogenic ★★★ same condition
LDLR c.1359-5C>G Likely pathogenic ★★★ same condition
LDLR c.1705+2T>C 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/ldlr-p-val800ile (accessed [today's date]).

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