Is B3GLCT p.Leu19Pro (c.56T>C) pathogenic?

B3GLCT p.Leu19Pro (c.56T>C) is classified Uncertain significance in B3GLCT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-01-24). AlphaMissense: likely benign (0.1294); Ultra-rare (popmax 0.0351%, nfe); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Leu19Pro (c.56T>C)?

B3GLCT p.Leu19Pro (c.56T>C) is associated with Inborn genetic diseases, Peters plus syndrome (ClinVar).

How common is B3GLCT p.Leu19Pro (c.56T>C) in the general population?

B3GLCT p.Leu19Pro (c.56T>C) is ultra-rare (popmax 0.0351%, nfe) (gnomAD).

What do computational predictors say about B3GLCT p.Leu19Pro (c.56T>C)?

AlphaMissense predicts likely benign (score 0.1294) — an in-silico prediction, not a clinical call.

B3GLCT p.Leu19Pro

c.56T>C · rs999173078 · VCV574845

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1294 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1294	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 0.47, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	24.7	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 0.0351% European (non-Finnish) · 367/1,045,876 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0309%

Overall 0.0279% 379/1,359,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0351%	2,850
Remaining individualsnot grpmax-eligible	0.0163%	6,144
African / African-American	0.00611%	16,362

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: B3GLCT
Protein: p.Leu19Pro
Coding: c.56T>C
MANE Select: NM_194318
dbSNP: rs999173078
Type: single nucleotide variant
Location: chr13:31200140 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB

Full B3GLCT 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

Also linked: Peters plus syndrome

Similar variants

B3GLCT c.459+1G>A Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.660+1G>A Pathogenic ★★ same condition
B3GLCT p.Tyr380Ter Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.*1752C>T Uncertain significance ★★ same condition
B3GLCT p.Arg377His Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asn243Ser Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Asn Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Tyr 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/b3glct-p-leu19pro (accessed [today's date]).

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