Is B4GALNT4 p.Arg780Pro (c.2339G>C) pathogenic?

B4GALNT4 p.Arg780Pro (c.2339G>C) is classified Uncertain significance in B4GALNT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: ambiguous (0.3817); Very rare (popmax 0.000599%, nfe).

How common is B4GALNT4 p.Arg780Pro (c.2339G>C) in the general population?

B4GALNT4 p.Arg780Pro (c.2339G>C) is very rare (popmax 0.000599%, nfe) (gnomAD).

What do computational predictors say about B4GALNT4 p.Arg780Pro (c.2339G>C)?

AlphaMissense predicts ambiguous (score 0.3817) — an in-silico prediction, not a clinical call.

B4GALNT4 p.Arg780Pro

c.2339G>C · rs996140395 · VCV2335849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000599%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3817	ambiguous
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.075 · regional, not allelic
Overall
CADD	23.9	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 0.000599% European (non-Finnish) · 7/1,169,476 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000441% 7/1,587,266 alleles · very 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: B4GALNT4
Protein: p.Arg780Pro
Coding: c.2339G>C
MANE Select: NM_178537
dbSNP: rs996140395
Type: single nucleotide variant
Location: chr11:379552 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.89

Full B4GALNT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B4GALNT4 p.Asn430Ser Benign ★★ same type
B4GALNT4 p.Pro160= Benign ★★ same type
B4GALNT4 p.Ala133Thr Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala204Ser Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala208Gly Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala219Val Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala294Val Uncertain significance ★ ⚠ same type
B4GALNT4 p.Ala345Val 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/b4galnt4-p-arg780pro (accessed [today's date]).

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