Is LTBP2 p.Ser1007Ile (c.3020G>T) pathogenic?

LTBP2 p.Ser1007Ile (c.3020G>T) is classified Uncertain significance in LTBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00263%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LTBP2 p.Ser1007Ile (c.3020G>T)?

LTBP2 p.Ser1007Ile (c.3020G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP2 p.Ser1007Ile (c.3020G>T) in the general population?

LTBP2 p.Ser1007Ile (c.3020G>T) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about LTBP2 p.Ser1007Ile (c.3020G>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

LTBP2 p.Ser1007Ile

c.3020G>T · rs1334220636 · VCV2479252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -3.8, phastCons 0.088
Regional constraint	o/e 0.94	unconstrained · MANE · 107 kb · p 0.013 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,179,964 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00226% 33/1,461,542 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	38,063
Admixed American	0.00167%	60,034
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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: LTBP2
Protein: p.Ser1007Ile
Coding: c.3020G>T
MANE Select: NM_000428
dbSNP: rs1334220636
Type: single nucleotide variant
Location: chr14:74511253 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 1007: the egf-like 7; calcium-binding domain; a disulfide bond

Full LTBP2 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

LTBP2 p.Ala1204Thr Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1354Val Uncertain significance ★★ same condition
LTBP2 p.Ala1359Val Uncertain significance ★★ same condition
LTBP2 p.Ala141Gly Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1421Val Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1734Val Uncertain significance ★★ same condition
LTBP2 p.Ala1767Val Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala451Asp 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/ltbp2-p-ser1007ile (accessed [today's date]).

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