Is LINS1 p.Ile554Val (c.1660A>G) pathogenic?

LINS1 p.Ile554Val (c.1660A>G) is classified Uncertain significance in LINS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-24). AlphaMissense: likely benign (0.0677); Very rare (popmax 0.00768%, sas); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Ile554Val (c.1660A>G)?

LINS1 p.Ile554Val (c.1660A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Ile554Val (c.1660A>G) in the general population?

LINS1 p.Ile554Val (c.1660A>G) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about LINS1 p.Ile554Val (c.1660A>G)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

LINS1 p.Ile554Val

c.1660A>G · rs777837713 · VCV1799621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.35	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -4.8	GERP -5
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

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000743% 12/1,614,068 alleles · very rare exomes 11/1,461,860 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
African / African-American	0.00267%	37,465
European (non-Finnish)	0.000254%	393,340

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.Ile554Val
Coding: c.1660A>G
MANE Select: NM_001040616
dbSNP: rs777837713
Type: single nucleotide variant
Location: chr15:100569852 (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-ile554val (accessed [today's date]).

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