Is B3GNT6 p.Ser247Pro (c.739T>C) pathogenic?

B3GNT6 p.Ser247Pro (c.739T>C) is classified Uncertain significance in B3GNT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely pathogenic (0.6618); Ultra-rare (popmax 0.066%, mid).

How common is B3GNT6 p.Ser247Pro (c.739T>C) in the general population?

B3GNT6 p.Ser247Pro (c.739T>C) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about B3GNT6 p.Ser247Pro (c.739T>C)?

AlphaMissense predicts likely pathogenic (score 0.6618) — an in-silico prediction, not a clinical call.

B3GNT6 p.Ser247Pro

c.739T>C · rs760180919 · VCV2402652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6618	likely pathogenic
REVEL	0.134	moderately benign-leaning
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4
Overall
CADD	1.498	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 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0359%

Overall 0.00415% 66/1,590,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
Admixed American	0.0562%	1,779
Remaining individualsnot grpmax-eligible	0.00645%	15,503
African / African-American	0.00268%	37,354
East Asian	0.00225%	44,398
European (non-Finnish)	0.00179%	56,012
South Asian	0.00112%	89,534

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: B3GNT6
Protein: p.Ser247Pro
Coding: c.739T>C
MANE Select: NM_006876 · reported on NM_138706
dbSNP: rs760180919
Type: single nucleotide variant
Location: chr11:77040290 (GRCh38)
Structure: AlphaFold pLDDT 88.46

Full B3GNT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B3GNT6 p.Ser247Cys Uncertain significance ★ ⚠ same residue
B4GAT1 p.Ala126Val Uncertain significance ★★ ⚠ same type
B4GAT1 p.Ala154Ser Uncertain significance ★★ ⚠ same type
B4GAT1 p.Ala379Gly Uncertain significance ★★ ⚠ same type
B4GAT1 p.Ala75Thr Uncertain significance ★★ ⚠ same type
B4GAT1 p.Arg341His Uncertain significance ★★ same type
B4GAT1 p.Arg414Cys Uncertain significance ★★ ⚠ same type
B4GAT1 p.Asp91Asn Uncertain significance ★★ ⚠ same type

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/b3gnt6-p-ser247pro (accessed [today's date]).

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