Is LINS1 p.Ile29Val (c.85A>G) pathogenic?

LINS1 p.Ile29Val (c.85A>G) is classified Benign in LINS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.0656); Common (popmax 47.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Ile29Val (c.85A>G)?

LINS1 p.Ile29Val (c.85A>G) is associated with Inborn genetic diseases (ClinVar).

What do computational predictors say about LINS1 p.Ile29Val (c.85A>G)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

LINS1 p.Ile29Val

Q: How common is LINS1 p.Ile29Val (c.85A>G) in the general population?

LINS1 p.Ile29Val (c.85A>G) is common (popmax 47.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.85A>G · rs11247226 · VCV587785

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 47.5%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.9	GERP -5.4
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.017 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.5% European (non-Finnish) · 558,453/1,175,612 alleles

Filtering AF 47.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.4%

Overall 43.6% 700,635/1,608,252 alleles · common exomes 645,435/1,456,230 · genomes 55,200/152,022 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	47.5%	2
Amishnot grpmax-eligible	42.7%	2
Remaining individualsnot grpmax-eligible	41.8%	2
Finnishnot grpmax-eligible	41.1%	2
Middle Eastern	39.3%	3
South Asian	38.6%	3
Ashkenazi Jewishnot grpmax-eligible	38%	3
East Asian	25.8%	4
African / African-American	21.9%	5
Admixed American	21.7%	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.Ile29Val
Coding: c.85A>G
MANE Select: NM_001040616
dbSNP: rs11247226
Type: single nucleotide variant
Location: chr15:100580758 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 29: a UniProt-annotated variant site (in)

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-ile29val (accessed [today's date]).

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