Is B3GLCT p.Phe441Leu (c.1323C>G) pathogenic?

B3GLCT p.Phe441Leu (c.1323C>G) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: likely pathogenic (0.9466); Ultra-rare (popmax 0.09%, sas); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Phe441Leu (c.1323C>G)?

B3GLCT p.Phe441Leu (c.1323C>G) is associated with Inborn genetic diseases (ClinVar).

How common is B3GLCT p.Phe441Leu (c.1323C>G) in the general population?

B3GLCT p.Phe441Leu (c.1323C>G) is ultra-rare (popmax 0.09%, sas) (gnomAD).

What do computational predictors say about B3GLCT p.Phe441Leu (c.1323C>G)?

AlphaMissense predicts likely pathogenic (score 0.9466) — an in-silico prediction, not a clinical call.

B3GLCT p.Phe441Leu

c.1323C>G · rs547723685 · VCV2594582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9466 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9466	likely pathogenic
REVEL	0.581	indeterminate
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.48, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% South Asian · 82/91,084 alleles

Filtering AF 0.0743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.00514% 83/1,614,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Phe441Leu
Coding: c.1323C>G
MANE Select: NM_194318
dbSNP: rs547723685
Type: single nucleotide variant
Location: chr13:31323889 (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
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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-phe441leu (accessed [today's date]).

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