Is B3GLCT p.Gln76Pro (c.227A>C) pathogenic?

B3GLCT p.Gln76Pro (c.227A>C) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.2305); Ultra-rare (popmax 0.0334%, afr); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Gln76Pro (c.227A>C)?

B3GLCT p.Gln76Pro (c.227A>C) is associated with Inborn genetic diseases (ClinVar).

How common is B3GLCT p.Gln76Pro (c.227A>C) in the general population?

B3GLCT p.Gln76Pro (c.227A>C) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

What do computational predictors say about B3GLCT p.Gln76Pro (c.227A>C)?

AlphaMissense predicts likely benign (score 0.2305) — an in-silico prediction, not a clinical call.

B3GLCT p.Gln76Pro

c.227A>C · VCV3815376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2305 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2305	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -15.24	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 4.4	GERP 0.84, phastCons 0.37
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	21.5	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 0.0334% African / African-American · 25/74,914 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00155% 25/1,613,634 alleles · ultra-rare

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.Gln76Pro
Coding: c.227A>C
MANE Select: NM_194318
Type: single nucleotide variant
Location: chr13:31229251 (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

Similar variants

B3GLCT c.459+1G>A Pathogenic/Likely pathogenic ★★ same condition
B3GLCT p.Arg377His Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Asn Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Tyr Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp484Gly Uncertain significance ★★ ⚠ same condition
B3GLCT p.Glu43Asp Uncertain significance ★★ ⚠ same condition
B3GLCT p.Gly229Asp Uncertain significance ★★ ⚠ same condition
B3GLCT p.Gly379Ser 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-gln76pro (accessed [today's date]).

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