Is B3GLCT p.Ile286Phe (c.856A>T) pathogenic?

B3GLCT p.Ile286Phe (c.856A>T) is classified Uncertain significance in B3GLCT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-06). AlphaMissense: likely benign (0.2748); Ultra-rare (popmax 0.025%, amr); Associated with Peters plus syndrome.

What condition is associated with B3GLCT p.Ile286Phe (c.856A>T)?

B3GLCT p.Ile286Phe (c.856A>T) is associated with Peters plus syndrome (ClinVar).

How common is B3GLCT p.Ile286Phe (c.856A>T) in the general population?

B3GLCT p.Ile286Phe (c.856A>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about B3GLCT p.Ile286Phe (c.856A>T)?

AlphaMissense predicts likely benign (score 0.2748) — an in-silico prediction, not a clinical call.

B3GLCT p.Ile286Phe

c.856A>T · rs116754126 · VCV1977735

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peters plus syndrome

Computational evidence

Protein change
AlphaMissense	0.2748	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -10.01	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 5.4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	22.7	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 0.025% Admixed American · 15/59,960 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00107% 17/1,584,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,997
Remaining individualsnot grpmax-eligible	0.00163%	61,444
European (non-Finnish)	8.67e-05%	1,153,391

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.Ile286Phe
Coding: c.856A>T
MANE Select: NM_194318
dbSNP: rs116754126
Type: single nucleotide variant
Location: chr13:31284653 (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

Peters plus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GLCT p.Ile286Val Uncertain significance ★★ ⚠ same residue
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

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-ile286phe (accessed [today's date]).

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