Is LPL p.His71= (c.213C>T) pathogenic?

LPL p.His71= (c.213C>T) is classified Likely benign in LPL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0516%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LPL p.His71= (c.213C>T)?

LPL p.His71= (c.213C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LPL p.His71= (c.213C>T) in the general population?

LPL p.His71= (c.213C>T) is ultra-rare (popmax 0.0516%, amr) (gnomAD).

LPL p.His71=

c.213C>T · rs11542065 · VCV1100360

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, amr)

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 0.56	GERP -1.2, phastCons 1
Overall
CADD	8.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0516% Admixed American · 31/60,022 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.0131% 211/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0516%	1,936
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.0142%	7,024
African / African-American	0.004%	25,007

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: LPL
Protein: p.His71=
Coding: c.213C>T
MANE Select: NM_000237
dbSNP: rs11542065
Type: single nucleotide variant
Location: chr8:19948304 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 71: a β-strand; a UniProt-annotated variant site (in)

Full LPL 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

Similar variants

LPL p.His71Gln Benign/Likely benign ★★ same residue
LPL c.1019-2A>T Pathogenic ★★ same condition
LPL c.1139+1G>A Likely pathogenic ★★ same condition
LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same condition
LPL c.249+1G>A Pathogenic ★★ same condition
LPL p.Ala98Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
LPL p.Arg197Cys Likely pathogenic ★★ ⚠ same condition
LPL p.Asp277Asn Pathogenic/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/lpl-p-his71 (accessed [today's date]).

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