Is LINS1 p.Ala331Val (c.992C>T) pathogenic?

LINS1 p.Ala331Val (c.992C>T) is classified Benign in LINS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0944); Common (popmax 7.41%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with LINS1 p.Ala331Val (c.992C>T)?

LINS1 p.Ala331Val (c.992C>T) is associated with Inborn genetic diseases (ClinVar).

What do computational predictors say about LINS1 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

LINS1 p.Ala331Val

Q: How common is LINS1 p.Ala331Val (c.992C>T) in the general population?

LINS1 p.Ala331Val (c.992C>T) is common (popmax 7.41%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.992C>T · rs34967129 · VCV588321

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.41%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.012	GERP -1.8
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.017 · regional, not allelic
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.41% African / African-American · 5,558/75,036 alleles

Filtering AF 7.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.18%

Overall 0.401% 6,472/1,614,152 alleles · common exomes 3,268/1,461,864 · genomes 3,204/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.41%	14
Remaining individualsnot grpmax-eligible	0.488%	205
Admixed American	0.483%	207
Middle Eastern	0.346%	289
South Asian	0.0285%	3,503
European (non-Finnish)	0.0231%	4,338

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.Ala331Val
Coding: c.992C>T
MANE Select: NM_001040616
dbSNP: rs34967129
Type: single nucleotide variant
Location: chr15:100573881 (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.Ala331= Likely 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-ala331val (accessed [today's date]).

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