Is LINS1 p.Ser376= (c.1128T>C) pathogenic?

LINS1 p.Ser376= (c.1128T>C) 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.Ser376= (c.1128T>C)?

LINS1 p.Ser376= (c.1128T>C) is associated with Inborn genetic diseases (ClinVar).

LINS1 p.Ser376=

Q: How common is LINS1 p.Ser376= (c.1128T>C) in the general population?

LINS1 p.Ser376= (c.1128T>C) is common (popmax 47.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1128T>C · rs12592868 · VCV587782

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -2.5
Overall
CADD	4.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.5% European (non-Finnish) · 560,138/1,179,132 alleles

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

Overall 44% 710,082/1,613,058 alleles · common exomes 650,888/1,460,952 · genomes 59,194/152,106 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	47.5%	2
Amishnot grpmax-eligible	42.7%	2
Remaining individualsnot grpmax-eligible	42.3%	2
Finnishnot grpmax-eligible	41.1%	2
Middle Eastern	39.3%	3
South Asian	38.3%	3
Ashkenazi Jewishnot grpmax-eligible	38.1%	3
African / African-American	31.2%	3
East Asian	25.7%	4
Admixed American	22.3%	4

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.Ser376=
Coding: c.1128T>C
MANE Select: NM_001040616
dbSNP: rs12592868
Type: single nucleotide variant
Location: chr15:100573745 (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-ser376 (accessed [today's date]).

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