Is B3GLCT p.His323Arg (c.968A>G) pathogenic?

B3GLCT p.His323Arg (c.968A>G) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-25). AlphaMissense: likely pathogenic (0.9687); Absent from gnomAD v4.1; Associated with Peters plus syndrome.

What condition is associated with B3GLCT p.His323Arg (c.968A>G)?

B3GLCT p.His323Arg (c.968A>G) is associated with Peters plus syndrome (ClinVar).

How common is B3GLCT p.His323Arg (c.968A>G) in the general population?

B3GLCT p.His323Arg (c.968A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about B3GLCT p.His323Arg (c.968A>G)?

AlphaMissense predicts likely pathogenic (score 0.9687) — an in-silico prediction, not a clinical call.

B3GLCT p.His323Arg

c.968A>G · rs1566082139 · VCV566991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Peters plus syndrome

Computational evidence

Protein change
AlphaMissense	0.9687	likely pathogenic · top 8% in B3GLCT
REVEL	0.641	indeterminate
SaProt	LLR -16.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: B3GLCT
Protein: p.His323Arg
Coding: c.968A>G
MANE Select: NM_194318
dbSNP: rs1566082139
Type: single nucleotide variant
Location: chr13:31286723 (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-his323arg (accessed [today's date]).

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