Is LDLR p.Cys313= (c.939C>T) pathogenic?

LDLR p.Cys313= (c.939C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-17). Ultra-rare (popmax 0.0586%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Cys313= (c.939C>T)?

LDLR p.Cys313= (c.939C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Cys313= (c.939C>T) in the general population?

LDLR p.Cys313= (c.939C>T) is ultra-rare (popmax 0.0586%, eas) (gnomAD).

LDLR p.Cys313=

c.939C>T · rs13306512 · VCV1766789

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0586%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.7
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0586% East Asian · 26/44,372 alleles

Filtering AF 0.041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.00274% 44/1,605,082 alleles · ultra-rare exomes 42/1,453,096 · genomes 2/151,986 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0586%	1,707
Finnishnot grpmax-eligible	0.0095%	10,526
European (non-Finnish)	0.00102%	97,856

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.Cys313=
Coding: c.939C>T
MANE Select: NM_000527
dbSNP: rs13306512
Type: single nucleotide variant
Location: chr19:11107513 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 313: the ldl-receptor class a 7 domain; a UniProt-annotated variant site (in fhcl1 and); a disulfide bond

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.Cys313Arg Likely pathogenic ★★★ same residue
LDLR p.Cys313Gly Likely pathogenic ★★ same residue
LDLR p.Cys313Ter Pathogenic ★★ same residue
LDLR p.Cys313Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Cys313Ser Uncertain significance ⚠ same residue
LDLR p.Cys313Tyr Pathogenic/Likely pathogenic ★★ same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>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-cys313 (accessed [today's date]).

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