Is LDLR p.Pro341= (c.1023C>T) pathogenic?

LDLR p.Pro341= (c.1023C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-12-31). Very rare (popmax 0.00667%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Pro341= (c.1023C>T)?

LDLR p.Pro341= (c.1023C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Pro341= (c.1023C>T) in the general population?

LDLR p.Pro341= (c.1023C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

LDLR p.Pro341=

c.1023C>T · rs376267007 · VCV1101310

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

Cardiovascular phenotype

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 -11	GERP -4.9
Overall
CADD	1.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,966 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.0044% 71/1,613,658 alleles · very rare exomes 65/1,461,516 · genomes 6/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,991
European (non-Finnish)	0.00525%	19,032
African / African-American	0.00267%	37,461
East Asian	0.00223%	44,886
South Asian	0.0022%	45,544

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.Pro341=
Coding: c.1023C>T
MANE Select: NM_000527
dbSNP: rs376267007
Type: single nucleotide variant
Location: chr19:11110734 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 341: the egf-like 1 domain; a β-strand

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.Pro341Arg Likely benign ★ ⚠ 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
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

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-pro341 (accessed [today's date]).

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