Is B4GALNT2 p.Val331Phe (c.991G>T) pathogenic?

B4GALNT2 p.Val331Phe (c.991G>T) is classified Uncertain significance in B4GALNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely pathogenic (0.8541); Very rare (popmax 0.00223%, eas).

How common is B4GALNT2 p.Val331Phe (c.991G>T) in the general population?

B4GALNT2 p.Val331Phe (c.991G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about B4GALNT2 p.Val331Phe (c.991G>T)?

AlphaMissense predicts likely pathogenic (score 0.8541) — an in-silico prediction, not a clinical call.

B4GALNT2 p.Val331Phe

c.991G>T · VCV3259164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8541	likely pathogenic · top 9% in B4GALNT2
REVEL	0.723	pathogenic-leaning
SaProt	LLR -14.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 37 kb · p 0.21 · regional, not allelic
Overall
CADD	31.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V391F vs ClinVar V331F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.2e-05% 1/1,614,058 alleles · very rare exomes 1/1,461,836 · genomes 0/152,222 · joint denominator

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: B4GALNT2
Protein: p.Val331Phe
Coding: c.991G>T
MANE Select: NM_001159387
Type: single nucleotide variant
Location: chr17:49166150 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.66

Full B4GALNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B4GALNT2 c.954+5G>A Benign ★★ same type
B4GALNT2 p.Arg463Trp Benign ★★ same type
B4GALNT2 p.Cys406Arg Benign ★★ same type
B4GALNT2 p.Gly4= Likely benign ★★ same type
B4GALNT2 c.14+245G>A Uncertain significance ★ ⚠ same type
B4GALNT2 c.14+269C>T Uncertain significance ★ ⚠ same type
B4GALNT2 c.14+278G>A Uncertain significance ★ ⚠ same type
B4GALNT2 c.14+296C>T 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/b4galnt2-p-val331phe (accessed [today's date]).

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