Is LTBP2 p.Ala7Val (c.20C>T) pathogenic?

LTBP2 p.Ala7Val (c.20C>T) is classified Benign in LTBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0915); Rare (popmax 0.177%, sas).

How common is LTBP2 p.Ala7Val (c.20C>T) in the general population?

LTBP2 p.Ala7Val (c.20C>T) is rare (popmax 0.177%, sas) (gnomAD).

What do computational predictors say about LTBP2 p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

LTBP2 p.Ala7Val

c.20C>T · rs781543497 · VCV2758132

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.177%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -7.39	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 2.4	GERP 0.15, phastCons 0.94
Regional constraint	o/e 0.94	unconstrained · MANE · 107 kb · p 0.013 · regional, not allelic
Overall
CADD	15.58	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 0.177% South Asian · 158/89,398 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.0102% 162/1,586,234 alleles · rare exomes 154/1,433,926 · genomes 8/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.177%	566
Middle Eastern	0.0198%	5,050
Remaining individualsnot grpmax-eligible	0.00326%	30,657
European (non-Finnish)	8.55e-05%	1,170,187

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_000428
dbSNP: rs781543497
Type: single nucleotide variant
Location: chr14:74611925 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33

Full LTBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LTBP2 p.Ala7= Conflicting classifications of pathogenicity ★ same residue
LTBP3 p.Ala7Ser Uncertain significance ★ ⚠ same residue
LTBP3 p.Ala7Thr Uncertain significance ★ ⚠ same residue
LTBP2 c.2389-2A>G Likely pathogenic ★★ same type
LTBP2 c.2659+2T>C Likely pathogenic ★★ same type
LTBP2 c.2789-1G>A Likely pathogenic ★★ same type
LTBP2 c.2789-2A>T Likely pathogenic ★★ same type
LTBP2 c.3652+1G>A Likely pathogenic ★★ same type

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-ala7val (accessed [today's date]).

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