Is LINS1 p.Phe220= (c.660C>T) pathogenic?

LINS1 p.Phe220= (c.660C>T) is classified Benign in LINS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). 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.Phe220= (c.660C>T)?

LINS1 p.Phe220= (c.660C>T) is associated with Inborn genetic diseases (ClinVar).

LINS1 p.Phe220=

Q: How common is LINS1 p.Phe220= (c.660C>T) in the general population?

LINS1 p.Phe220= (c.660C>T) is common (popmax 47.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.660C>T · rs8039437 · VCV587790

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

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

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 0.002	GERP -5.3, phastCons 0.016
Overall
CADD	8.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.5% European (non-Finnish) · 557,208/1,174,172 alleles

Filtering AF 47.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.3%

Overall 43.8% 703,931/1,607,152 alleles · common exomes 646,121/1,455,104 · genomes 57,810/152,048 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	47.5%	2
Amishnot grpmax-eligible	43%	2
Remaining individualsnot grpmax-eligible	42%	2
Finnishnot grpmax-eligible	41.1%	2
Middle Eastern	39.1%	3
South Asian	38.2%	3
Ashkenazi Jewishnot grpmax-eligible	38.1%	3
African / African-American	27.9%	4
East Asian	25.7%	4
Admixed American	22.1%	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.Phe220=
Coding: c.660C>T
MANE Select: NM_001040616
dbSNP: rs8039437
Type: single nucleotide variant
Location: chr15:100574213 (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-phe220 (accessed [today's date]).

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