Is B3GLCT p.Arg337His (c.1010G>A) pathogenic?

B3GLCT p.Arg337His (c.1010G>A) is classified Conflicting classifications of pathogenicity in B3GLCT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0547); Rare (popmax 0.169%, eas); Associated with Peters plus syndrome.

What condition is associated with B3GLCT p.Arg337His (c.1010G>A)?

B3GLCT p.Arg337His (c.1010G>A) is associated with Peters plus syndrome (ClinVar).

How common is B3GLCT p.Arg337His (c.1010G>A) in the general population?

B3GLCT p.Arg337His (c.1010G>A) is rare (popmax 0.169%, eas) (gnomAD).

What do computational predictors say about B3GLCT p.Arg337His (c.1010G>A)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

B3GLCT p.Arg337His

c.1010G>A · rs199794968 · VCV385610

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peters plus syndrome

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -7.88	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 -0.013	GERP -3.9
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	9.444	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 0.169% East Asian · 76/44,854 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.0179% 288/1,613,278 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.493%	203
East Asiangrpmax	0.169%	590
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Admixed American	0.025%	3,997
African / African-American	0.00534%	18,711
European (non-Finnish)	0.00254%	39,320

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg337His
Coding: c.1010G>A
MANE Select: NM_194318
dbSNP: rs199794968
Type: single nucleotide variant
Location: chr13:31286765 (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 p.Arg337Cys Uncertain significance ★ ⚠ same residue
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

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-arg337his (accessed [today's date]).

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