Is B4GALNT4 p.Val125Met (c.373G>A) pathogenic?

B4GALNT4 p.Val125Met (c.373G>A) is classified Uncertain significance in B4GALNT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.6273); Very rare (popmax 0.00167%, amr).

How common is B4GALNT4 p.Val125Met (c.373G>A) in the general population?

B4GALNT4 p.Val125Met (c.373G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about B4GALNT4 p.Val125Met (c.373G>A)?

AlphaMissense predicts likely pathogenic (score 0.6273) — an in-silico prediction, not a clinical call.

B4GALNT4 p.Val125Met

c.373G>A · VCV4644982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6273	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -11.43	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.075 · regional, not allelic
Overall
CADD	29.1	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 0.00167% Admixed American · 1/59,970 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,611,908 alleles · very rare exomes 8/1,459,942 · genomes 0/151,966 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,970
Finnishnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.000509%	196,623

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.Val125Met
Coding: c.373G>A
MANE Select: NM_178537
Type: single nucleotide variant
Location: chr11:372876 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.89
Residue 125: the pa14 domain

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-val125met (accessed [today's date]).

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