Is LINS1 p.Phe512Ile (c.1534T>A) pathogenic?

LINS1 p.Phe512Ile (c.1534T>A) is classified Uncertain significance in LINS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-30). AlphaMissense: likely pathogenic (0.8035); Very rare (popmax 0.00186%, amr); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Phe512Ile (c.1534T>A)?

LINS1 p.Phe512Ile (c.1534T>A) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Phe512Ile (c.1534T>A) in the general population?

LINS1 p.Phe512Ile (c.1534T>A) is very rare (popmax 0.00186%, amr) (gnomAD).

What do computational predictors say about LINS1 p.Phe512Ile (c.1534T>A)?

AlphaMissense predicts likely pathogenic (score 0.8035) — an in-silico prediction, not a clinical call.

LINS1 p.Phe512Ile

c.1534T>A · rs777896839 · VCV1799604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8035	likely pathogenic · top 6% in LINS1
REVEL	0.321	indeterminate
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.017 · regional, not allelic
Overall
CADD	26.7	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 0.00186% Admixed American · 1/53,790 alleles

Overall 6.36e-05% 1/1,572,210 alleles · very rare exomes 1/1,419,856 · genomes 0/152,354 · joint denominator

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.Phe512Ile
Coding: c.1534T>A
MANE Select: NM_001040616
dbSNP: rs777896839
Type: single nucleotide variant
Location: chr15:100569978 (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-phe512ile (accessed [today's date]).

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