Is LDLR p.Ser212= (c.636C>T) pathogenic?

LDLR p.Ser212= (c.636C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-23). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Ser212= (c.636C>T)?

LDLR p.Ser212= (c.636C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia (ClinVar).

How common is LDLR p.Ser212= (c.636C>T) in the general population?

LDLR p.Ser212= (c.636C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

LDLR p.Ser212=

c.636C>T · rs538030445 · VCV920366

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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 -3.7	GERP -5.1
Overall
CADD	1.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,714 alleles · very rare exomes 4/1,461,398 · genomes 1/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
African / African-American	0.00133%	75,052
European (non-Finnish)	0.000254%	393,318

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.Ser212=
Coding: c.636C>T
MANE Select: NM_000527
dbSNP: rs538030445
Type: single nucleotide variant
Location: chr19:11105542 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 212: the 'binding to getah virus e1-e2 spike glycoproteins' region; an α-helix; the ldl-receptor class a 5 domain

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

Similar variants

LDLR p.Ser212Phe Uncertain significance ★★ ⚠ same residue
LDLR p.Ser212Cys Uncertain significance ★ ⚠ 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

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-ser212 (accessed [today's date]).

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