Is LINS1 p.Leu429= (c.1285C>T) pathogenic?

LINS1 p.Leu429= (c.1285C>T) is classified Benign/Likely benign in LINS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-12). Low-frequency (popmax 1.5%, afr); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Leu429= (c.1285C>T)?

LINS1 p.Leu429= (c.1285C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Leu429= (c.1285C>T) in the general population?

LINS1 p.Leu429= (c.1285C>T) is low-frequency (popmax 1.5%, afr) (gnomAD).

LINS1 p.Leu429=

c.1285C>T · rs141962847 · VCV589122

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.5%, afr)

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 3.1	GERP 1.1, phastCons 0.92
Overall
CADD	9.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.5% African / African-American · 1,128/75,054 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.0893% 1,441/1,614,208 alleles · low-frequency exomes 784/1,461,886 · genomes 657/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.5%	67
Middle Eastern	0.528%	189
Admixed American	0.122%	822
Remaining individualsnot grpmax-eligible	0.11%	906
South Asian	0.0176%	5,693
European (non-Finnish)	0.0104%	9,594

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.Leu429=
Coding: c.1285C>T
MANE Select: NM_001040616
dbSNP: rs141962847
Type: single nucleotide variant
Location: chr15:100572003 (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-leu429 (accessed [today's date]).

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