Is LDLR p.Val328= (c.984C>G) pathogenic?

LDLR p.Val328= (c.984C>G) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Very rare (popmax 0.0011%, sas); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Val328= (c.984C>G)?

LDLR p.Val328= (c.984C>G) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Val328= (c.984C>G) in the general population?

LDLR p.Val328= (c.984C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

LDLR p.Val328=

c.984C>G · rs776786267 · VCV2880319

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

familial hypercholesterolemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 1.4, phastCons 1
Overall
CADD	6.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 6.2e-05% 1/1,613,924 alleles · very rare exomes 1/1,461,618 · genomes 0/152,306 · 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: LDLR
Protein: p.Val328=
Coding: c.984C>G
MANE Select: NM_000527
dbSNP: rs776786267
Type: single nucleotide variant
Location: chr19:11110695 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 328: the egf-like 1 domain; a β-strand

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

Disease context

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLR p.Val328Ile 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.190+4A>T Likely pathogenic ★★★ same condition
LDLR c.2140+1G>A Pathogenic ★★★ same condition
LDLR c.2389+2T>G Pathogenic ★★★ same condition
LDLR c.313+1G>A 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-val328 (accessed [today's date]).

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