Is LPL p.Val60Leu (c.178G>T) pathogenic?

LPL p.Val60Leu (c.178G>T) is classified Uncertain significance in LPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely benign (0.1189); Very rare (popmax 0.00549%, sas).

How common is LPL p.Val60Leu (c.178G>T) in the general population?

LPL p.Val60Leu (c.178G>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about LPL p.Val60Leu (c.178G>T)?

AlphaMissense predicts likely benign (score 0.1189) — an in-silico prediction, not a clinical call.

LPL p.Val60Leu

c.178G>T · rs887595131 · VCV2577246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1189	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -3.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.22, phastCons 0.97
Regional constraint	o/e 1.09	unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,078 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000342% 5/1,461,864 alleles · very rare

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.Val60Leu
Coding: c.178G>T
MANE Select: NM_000237
dbSNP: rs887595131
Type: single nucleotide variant
Location: chr8:19948269 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 60: a disulfide bond

Full LPL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LPL c.1019-2A>T Pathogenic ★★ same type
LPL c.1019-3C>A Pathogenic/Likely pathogenic ★★ same type
LPL c.1139+1G>A Likely pathogenic ★★ same type
LPL c.1139+7A>G Likely pathogenic ★★ same type
LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same type
LPL c.249+1G>A Pathogenic ★★ same type
LPL c.89-1G>A Pathogenic/Likely pathogenic ★★ same type
LPL c.89-1G>C Pathogenic/Likely pathogenic ★★ same type

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-val60leu (accessed [today's date]).

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