Is LIPH p.Thr286= (c.858G>A) pathogenic?

LIPH p.Thr286= (c.858G>A) is classified Likely benign in LIPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Ultra-rare (popmax 0.0212%, nfe).

How common is LIPH p.Thr286= (c.858G>A) in the general population?

LIPH p.Thr286= (c.858G>A) is ultra-rare (popmax 0.0212%, nfe) (gnomAD).

LIPH p.Thr286=

c.858G>A · rs139327062 · VCV2892524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.4	GERP -3.6
Overall
CADD	0.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0212% European (non-Finnish) · 250/1,179,956 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0193% 311/1,614,056 alleles · ultra-rare exomes 294/1,461,812 · genomes 17/152,244 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0375%	2,667
Remaining individualsnot grpmax-eligible	0.0224%	4,464
European (non-Finnish)grpmax	0.0212%	4,720
South Asian	0.0198%	5,060
Middle Eastern	0.0165%	6,062
African / African-American	0.00267%	37,516
East Asian	0.00223%	44,882
Admixed American	0.00167%	60,016

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LIPH
Protein: p.Thr286=
Coding: c.858G>A
MANE Select: NM_139248
dbSNP: rs139327062
Type: single nucleotide variant
Location: chr3:185519170 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.89
Residue 286: a UniProt-annotated variant site (in arwh2)

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

Similar variants

LIPH p.Thr286Met Uncertain significance ★★ ⚠ same residue
LIPH p.Arg110Ter Pathogenic/Likely pathogenic ★★ same type
LIPH p.Cys246Ser Pathogenic/Likely pathogenic ★★ same type
LIPH p.His248Asn Pathogenic/Likely pathogenic ★★ same type
LIPH p.Ala180Gly Uncertain significance ★★ ⚠ same type
LIPH p.Arg110Leu Uncertain significance ★★ ⚠ same type
LIPH p.Ile336Met Uncertain significance ★★ ⚠ same type
LIPH c.1094+29C>T Benign ★★ 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/liph-p-thr286 (accessed [today's date]).

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