Is VLDLR p.Ile802Phe (c.2404A>T) pathogenic?

VLDLR p.Ile802Phe (c.2404A>T) is classified Uncertain significance in VLDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.096); Very rare (popmax 0.00169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VLDLR p.Ile802Phe (c.2404A>T)?

VLDLR p.Ile802Phe (c.2404A>T) is associated with Inborn genetic diseases (ClinVar).

How common is VLDLR p.Ile802Phe (c.2404A>T) in the general population?

VLDLR p.Ile802Phe (c.2404A>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about VLDLR p.Ile802Phe (c.2404A>T)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

VLDLR p.Ile802Phe

c.2404A>T · rs748800533 · VCV2378335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 32 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,179,964 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,613,950 alleles · very rare exomes 19/1,461,760 · genomes 1/152,190 · joint denominator

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: VLDLR
Protein: p.Ile802Phe
Coding: c.2404A>T
MANE Select: NM_003383
dbSNP: rs748800533
Type: single nucleotide variant
Location: chr9:2651942 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 27 PDB

Full VLDLR 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

VLDLR p.Ala195Thr Uncertain significance ★★ ⚠ same condition
VLDLR p.Arg165His Uncertain significance ★★ ⚠ same condition
VLDLR p.Arg276Pro Uncertain significance ★★ ⚠ same condition
VLDLR p.Arg279Gln Uncertain significance ★★ ⚠ same condition
VLDLR p.Arg613His Uncertain significance ★★ ⚠ same condition
VLDLR p.Arg656Cys Uncertain significance ★★ ⚠ same condition
VLDLR p.Asn741Ser Uncertain significance ★★ ⚠ same condition
VLDLR p.Asp220Asn 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/vldlr-p-ile802phe (accessed [today's date]).

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