Is B4GALNT3 p.Ser277Phe (c.830C>T) pathogenic?

B4GALNT3 p.Ser277Phe (c.830C>T) is classified Uncertain significance in B4GALNT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.6521); Absent from gnomAD v4.1.

How common is B4GALNT3 p.Ser277Phe (c.830C>T) in the general population?

B4GALNT3 p.Ser277Phe (c.830C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about B4GALNT3 p.Ser277Phe (c.830C>T)?

AlphaMissense predicts likely pathogenic (score 0.6521) — an in-silico prediction, not a clinical call.

B4GALNT3 p.Ser277Phe

c.830C>T · VCV4644958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6521 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6521	likely pathogenic
REVEL	0.457	indeterminate
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 17 kb · p 0.00032 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: B4GALNT3
Protein: p.Ser277Phe
Coding: c.830C>T
MANE Select: NM_173593
Type: single nucleotide variant
Location: chr12:548274 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.56
Residue 277: the pa14 domain

Full B4GALNT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B4GALNT3 p.Arg686= Benign ★★ same type
B4GALNT3 p.Glu441Asp Benign ★★ same type
B4GALNT3 p.Gly752Val Benign ★★ same type
B4GALNT3 p.His536Tyr Benign ★★ same type
B4GALNT3 c.1271-1G>C Likely pathogenic ★ same type
B4GALNT3 p.Ala158Ser Uncertain significance ★ ⚠ same type
B4GALNT3 p.Ala239Val Uncertain significance ★ ⚠ same type
B4GALNT3 p.Ala28Val 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/b4galnt3-p-ser277phe (accessed [today's date]).

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