Is LINS1 p.Asp633= (c.1899C>T) pathogenic?

LINS1 p.Asp633= (c.1899C>T) is classified Benign in LINS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). Common (popmax 56.4%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Asp633= (c.1899C>T)?

LINS1 p.Asp633= (c.1899C>T) is associated with Inborn genetic diseases (ClinVar).

LINS1 p.Asp633=

Q: How common is LINS1 p.Asp633= (c.1899C>T) in the general population?

LINS1 p.Asp633= (c.1899C>T) is common (popmax 56.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1899C>T · rs12460 · VCV587792

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 56.4%, mid) — 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 0.28	GERP -2.5, phastCons 0.72
Overall
CADD	8.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.4% Middle Eastern · 3,418/6,058 alleles

Filtering AF 55.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.8%

Overall 53.8% 867,570/1,612,298 alleles · common exomes 792,828/1,460,386 · genomes 74,742/151,912 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	58.7%	2
Ashkenazi Jewishnot grpmax-eligible	58.1%	2
Middle Easterngrpmax	56.4%	2
European (non-Finnish)	55.9%	2
Remaining individualsnot grpmax-eligible	54%	2
East Asian	52.1%	2
South Asian	50.1%	2
Finnishnot grpmax-eligible	49.1%	2
Admixed American	40.4%	2
African / African-American	38.7%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp633=
Coding: c.1899C>T
MANE Select: NM_001040616
dbSNP: rs12460
Type: single nucleotide variant
Location: chr15:100569613 (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-asp633 (accessed [today's date]).

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