Is LTBP4 p.Ala23= (c.69A>C) pathogenic?

LTBP4 p.Ala23= (c.69A>C) is classified Likely benign in LTBP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). AlphaMissense: likely benign (0.099); Very rare (popmax 0.000254%, nfe).

How common is LTBP4 p.Ala23= (c.69A>C) in the general population?

LTBP4 p.Ala23= (c.69A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about LTBP4 p.Ala23= (c.69A>C)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

LTBP4 p.Ala23=

c.69A>C · rs759267510 · VCV2994355

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -4.19	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 1.3	GERP -2.5, phastCons 0.3
Overall
CADD	16.53	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 0.000254% European (non-Finnish) · 3/1,179,756 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,570 alleles · very rare exomes 2/1,461,390 · genomes 1/152,180 · joint denominator

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: LTBP4
Protein: p.Ala23=
Coding: c.69A>C
MANE Select: NM_001042545 · reported on NM_003573
dbSNP: rs759267510
Type: single nucleotide variant
Location: chr19:40599249 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53

Full LTBP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LTBP4 p.Ala23Val Uncertain significance ★★ same residue
LTBP4 c.1307-2A>G Pathogenic/Likely pathogenic ★★ same type
LTBP4 p.Arg677Ter Pathogenic/Likely pathogenic ★★ same type
LTBP4 p.Arg691Ter Pathogenic ★★ same type
LTBP4 c.2944+5G>C Uncertain significance ★★ same type
LTBP4 c.3070+4C>T Uncertain significance ★★ same type
LTBP4 c.*121C>G Uncertain significance ★★ same type
LTBP4 p.Ala1090Thr Uncertain significance ★★ ⚠ 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/ltbp4-p-ala23 (accessed [today's date]).

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