Is LTBP4 p.Ser26= (c.78C>G) pathogenic?

LTBP4 p.Ser26= (c.78C>G) is classified Likely benign in LTBP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). Ultra-rare (popmax 0.0217%, amr).

How common is LTBP4 p.Ser26= (c.78C>G) in the general population?

LTBP4 p.Ser26= (c.78C>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

LTBP4 p.Ser26=

c.78C>G · rs188795613 · VCV1589757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

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 2.4	GERP -1.3, phastCons 1
Overall
CADD	17.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/59,968 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00093% 15/1,612,196 alleles · ultra-rare exomes 9/1,459,934 · genomes 6/152,262 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,613
Remaining individualsnot grpmax-eligible	0.00321%	31,197

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.Ser26=
Coding: c.78C>G
MANE Select: NM_001042545 · reported on NM_003573
dbSNP: rs188795613
Type: single nucleotide variant
Location: chr19:40599404 (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.Ser26Phe 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-ser26 (accessed [today's date]).

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