Is LINS1 p.Thr484= (c.1452A>T) pathogenic?

LINS1 p.Thr484= (c.1452A>T) is classified Benign in LINS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). Common (popmax 47.3%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Thr484= (c.1452A>T)?

LINS1 p.Thr484= (c.1452A>T) is associated with Inborn genetic diseases (ClinVar).

LINS1 p.Thr484=

Q: How common is LINS1 p.Thr484= (c.1452A>T) in the general population?

LINS1 p.Thr484= (c.1452A>T) is common (popmax 47.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1452A>T · rs2411836 · VCV587791

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 47.3%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -3.9	GERP -5.4
Overall
CADD	0.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.3% European (non-Finnish) · 549,306/1,161,796 alleles

Filtering AF 47.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.1%

Overall 43.7% 682,410/1,562,562 alleles · common exomes 624,942/1,410,564 · genomes 57,468/151,998 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	47.3%	2
Amishnot grpmax-eligible	43%	2
Remaining individualsnot grpmax-eligible	41.8%	2
Finnishnot grpmax-eligible	40.9%	2
Middle Eastern	38.8%	3
South Asian	37.5%	3
Ashkenazi Jewishnot grpmax-eligible	37.1%	3
African / African-American	27.1%	4
East Asian	25.6%	4
Admixed American	21.6%	5

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.Thr484=
Coding: c.1452A>T
MANE Select: NM_001040616
dbSNP: rs2411836
Type: single nucleotide variant
Location: chr15:100570060 (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-thr484 (accessed [today's date]).

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