Is LDLR p.Ala19Val (c.56C>T) pathogenic?

LDLR p.Ala19Val (c.56C>T) is classified Conflicting classifications of pathogenicity in LDLR (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-12-02). AlphaMissense: likely benign (0.1483); Very rare (popmax 0.0022%, sas); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Ala19Val (c.56C>T)?

LDLR p.Ala19Val (c.56C>T) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ala19Val (c.56C>T) in the general population?

LDLR p.Ala19Val (c.56C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about LDLR p.Ala19Val (c.56C>T)?

AlphaMissense predicts likely benign (score 0.1483) — an in-silico prediction, not a clinical call.

LDLR p.Ala19Val

c.56C>T · rs879254392 · VCV250985

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1483 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial hypercholesterolemia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1483	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.5	GERP -3
Regional constraint	o/e 1.00	unconstrained · MANE · 42 kb · p 0.91 · regional, not allelic
Overall
CADD	1.623	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 0.0022% South Asian · 2/90,912 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,612,090 alleles · very rare exomes 3/1,459,904 · genomes 0/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,456
European (non-Finnish)	8.48e-05%	1,179,679

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.Ala19Val
Coding: c.56C>T
MANE Select: NM_000527
dbSNP: rs879254392
Type: single nucleotide variant
Location: chr19:11089604 (GRCh38)

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

Also linked: hypercholesterolemia, familial, 1

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-ala19val (accessed [today's date]).

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