Is LINS1 p.Thr288= (c.864C>T) pathogenic?

LINS1 p.Thr288= (c.864C>T) is classified Conflicting classifications of pathogenicity in LINS1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2018-10-09). Rare (popmax 0.189%, afr); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Thr288= (c.864C>T)?

LINS1 p.Thr288= (c.864C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Thr288= (c.864C>T) in the general population?

LINS1 p.Thr288= (c.864C>T) is rare (popmax 0.189%, afr) (gnomAD).

LINS1 p.Thr288=

c.864C>T · rs150775570 · VCV211386

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.189%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.29	GERP -2, phastCons 0.83
Overall
CADD	6.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% African / African-American · 142/75,036 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.00985% 159/1,614,064 alleles · rare exomes 78/1,461,784 · genomes 81/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.189%	528
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.0133%	7,502

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: LINS1
Protein: p.Thr288=
Coding: c.864C>T
MANE Select: NM_001040616
dbSNP: rs150775570
Type: single nucleotide variant
Location: chr15:100574009 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

Full LINS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LINS1 c.1394+4A>G Uncertain significance ★★ same condition
LINS1 p.Ala338Val Uncertain significance ★★ ⚠ same condition
LINS1 p.Asn433Ser Uncertain significance ★★ ⚠ same condition
LINS1 p.Asp630Asn Uncertain significance ★★ ⚠ same condition
LINS1 p.Ile494Thr Uncertain significance ★★ ⚠ same condition
LINS1 p.Leu757Ter Uncertain significance ★★ same condition
LINS1 p.Met449Ile Uncertain significance ★★ ⚠ same condition
LINS1 p.Ala331Val Benign ★★ 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/lins1-p-thr288 (accessed [today's date]).

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