Is LDLR p.Ser177= (c.531G>A) pathogenic?

LDLR p.Ser177= (c.531G>A) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-16). Ultra-rare (popmax 0.0209%, sas); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Ser177= (c.531G>A)?

LDLR p.Ser177= (c.531G>A) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser177= (c.531G>A) in the general population?

LDLR p.Ser177= (c.531G>A) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

LDLR p.Ser177=

c.531G>A · rs555158224 · VCV440576

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

familial hypercholesterolemia

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 -20	GERP -5.1
Overall
CADD	0.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/91,084 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00242% 39/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0048%	20,835
African / African-American	0.004%	25,021
East Asian	0.00223%	44,888
European (non-Finnish)	0.000508%	196,673

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.Ser177=
Coding: c.531G>A
MANE Select: NM_000527
dbSNP: rs555158224
Type: single nucleotide variant
Location: chr19:11105437 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 177: a UniProt-annotated variant site (in fhcl1; pathogenic; puerto rico); the 'binding to getah virus e1-e2 spike glycoproteins' region; an α-helix; the ldl-receptor class a 4 domain

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

Similar variants

LDLR p.Ser177Leu Pathogenic ★★★ same residue
LDLR p.Ser177Pro Likely pathogenic ★ same residue
LDLR p.Ser177Trp 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.1705+2T>C Likely pathogenic ★★★ same condition
LDLR c.190+4A>T Likely 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-ser177 (accessed [today's date]).

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