Is LINS1 p.Pro434= (c.1302G>A) pathogenic?

LINS1 p.Pro434= (c.1302G>A) is classified Benign/Likely benign in LINS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-27). Rare (popmax 0.869%, afr); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Pro434= (c.1302G>A)?

LINS1 p.Pro434= (c.1302G>A) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Pro434= (c.1302G>A) in the general population?

LINS1 p.Pro434= (c.1302G>A) is rare (popmax 0.869%, afr) (gnomAD).

LINS1 p.Pro434=

c.1302G>A · rs148166631 · VCV587891

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.869%, 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 -8.6	GERP -5.7
Overall
CADD	1.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.869% African / African-American · 652/75,000 alleles

Filtering AF 0.814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.792%

Overall 0.0499% 806/1,614,120 alleles · rare exomes 424/1,461,886 · genomes 382/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.869%	115
Remaining individualsnot grpmax-eligible	0.101%	992
Middle Eastern	0.0825%	1,212
Admixed American	0.08%	1,250
South Asian	0.0121%	8,281
East Asian	0.00446%	22,440
European (non-Finnish)	0.00212%	47,201

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.Pro434=
Coding: c.1302G>A
MANE Select: NM_001040616
dbSNP: rs148166631
Type: single nucleotide variant
Location: chr15:100571986 (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 p.Pro434Leu Uncertain significance ★ ⚠ same residue
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

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-pro434 (accessed [today's date]).

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