Is B3GLCT p.Asp41His (c.121G>C) pathogenic?

B3GLCT p.Asp41His (c.121G>C) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.0819); Very rare (popmax 0.00383%, nfe); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Asp41His (c.121G>C)?

B3GLCT p.Asp41His (c.121G>C) is associated with Inborn genetic diseases (ClinVar).

How common is B3GLCT p.Asp41His (c.121G>C) in the general population?

B3GLCT p.Asp41His (c.121G>C) is very rare (popmax 0.00383%, nfe) (gnomAD).

What do computational predictors say about B3GLCT p.Asp41His (c.121G>C)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

B3GLCT p.Asp41His

c.121G>C · rs755028268 · VCV2525261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00383%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	19.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00383% European (non-Finnish) · 42/1,095,446 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00254%

Overall 0.00283% 43/1,520,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00383%	26,082
Remaining individualsnot grpmax-eligible	0.00169%	59,240

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.Asp41His
Coding: c.121G>C
MANE Select: NM_194318
dbSNP: rs755028268
Type: single nucleotide variant
Location: chr13:31222952 (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-asp41his (accessed [today's date]).

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