Is B3GLCT p.Ala222= (c.666C>G) pathogenic?

B3GLCT p.Ala222= (c.666C>G) is classified Likely benign in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Very rare (popmax 0.00267%, afr); Associated with Peters plus syndrome.

What condition is associated with B3GLCT p.Ala222= (c.666C>G)?

B3GLCT p.Ala222= (c.666C>G) is associated with Peters plus syndrome (ClinVar).

How common is B3GLCT p.Ala222= (c.666C>G) in the general population?

B3GLCT p.Ala222= (c.666C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

B3GLCT p.Ala222=

c.666C>G · VCV3653520

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Peters plus syndrome

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 -1.4	GERP -0.21
Overall
CADD	6.176	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,457
European (non-Finnish)	0.000593%	168,577

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.Ala222=
Coding: c.666C>G
MANE Select: NM_194318
Type: single nucleotide variant
Location: chr13:31274514 (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 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-ala222 (accessed [today's date]).

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