Is LINS1 p.Met82fs (c.244_248del) pathogenic?

LINS1 p.Met82fs (c.244248del) is classified Likely pathogenic in LINS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). Very rare (popmax 0.00203%, nfe).

How common is LINS1 p.Met82fs (c.244_248del) in the general population?

LINS1 p.Met82fs (c.244_248del) is very rare (popmax 0.00203%, nfe) (gnomAD).

LINS1 p.Met82fs

c.244_248del · rs767760664 · VCV504353

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.27	GERP -2.1
Overall
CADD	18.49	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,958 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,613,894 alleles · very rare exomes 23/1,461,728 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,165
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Met82fs
Coding: c.244_248del
MANE Select: NM_001040616
dbSNP: rs767760664
Type: Deletion
Location: chr15:100580595 (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

Similar variants

LINS1 p.Gly558fs Pathogenic ★★ same type
LINS1 p.His328fs Pathogenic ★★ same type
LINS1 c.1219_1222+1del Pathogenic ★ same type
LINS1 p.Arg440fs Likely pathogenic ★ same type
LINS1 p.Arg576fs Likely pathogenic ★ same type
LINS1 p.Arg584fs Likely pathogenic ★ same type
LINS1 p.Arg711_Ile712insTer Likely pathogenic ★ same type
LINS1 p.Asn487fs Pathogenic ★ same type

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-met82fs (accessed [today's date]).

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