Is LINS1 p.Gln398= (c.1194A>G) pathogenic?

LINS1 p.Gln398= (c.1194A>G) is classified Benign/Likely benign in LINS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.448%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Gln398= (c.1194A>G)?

LINS1 p.Gln398= (c.1194A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Gln398= (c.1194A>G) in the general population?

LINS1 p.Gln398= (c.1194A>G) is rare (popmax 0.448%, nfe) (gnomAD).

LINS1 p.Gln398=

c.1194A>G · rs138347314 · VCV211378

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.448%, nfe)

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 -0.78	GERP -5.7, phastCons 0.001
Overall
CADD	1.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.448% European (non-Finnish) · 5,272/1,177,004 alleles

Filtering AF 0.438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.434%

Overall 0.353% 5,677/1,608,822 alleles · rare exomes 5,331/1,456,486 · genomes 346/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.448%	223
Remaining individualsnot grpmax-eligible	0.238%	421
Admixed American	0.187%	534
Ashkenazi Jewishnot grpmax-eligible	0.126%	796
Finnishnot grpmax-eligible	0.0828%	1,207
African / African-American	0.0696%	1,437
East Asian	0.00446%	22,433
South Asian	0.00222%	45,146

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.Gln398=
Coding: c.1194A>G
MANE Select: NM_001040616
dbSNP: rs138347314
Type: single nucleotide variant
Location: chr15:100573679 (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-gln398 (accessed [today's date]).

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