Is LINS1 p.Ala331= (c.993G>A) pathogenic?

LINS1 p.Ala331= (c.993G>A) is classified Likely benign in LINS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-31). Rare (popmax 0.145%, eas); Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Ala331= (c.993G>A)?

LINS1 p.Ala331= (c.993G>A) is associated with Inborn genetic diseases (ClinVar).

How common is LINS1 p.Ala331= (c.993G>A) in the general population?

LINS1 p.Ala331= (c.993G>A) is rare (popmax 0.145%, eas) (gnomAD).

LINS1 p.Ala331=

c.993G>A · rs767030288 · VCV589373

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

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 -2.3	GERP -5.7
Overall
CADD	1.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% East Asian · 65/44,886 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00669% 108/1,614,206 alleles · rare exomes 96/1,461,874 · genomes 12/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	691
African / African-American	0.00666%	15,012
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.005%	20,011
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00254%	39,334

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.Ala331=
Coding: c.993G>A
MANE Select: NM_001040616
dbSNP: rs767030288
Type: single nucleotide variant
Location: chr15:100573880 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 331: a UniProt-annotated variant site (in)

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 p.Ala331Val Benign ★★ same residue
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

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-ala331 (accessed [today's date]).

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