Is B3GNT8 p.Val188= (c.564G>A) pathogenic?

B3GNT8 p.Val188= (c.564G>A) is classified Benign in B3GNT8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-05). Common (popmax 60.9%, nfe) — too common for a highly-penetrant pathogenic allele.

B3GNT8 p.Val188=

Q: How common is B3GNT8 p.Val188= (c.564G>A) in the general population?

B3GNT8 p.Val188= (c.564G>A) is common (popmax 60.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.564G>A · rs284661 · VCV1248115

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 60.9%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -2.4
Overall
CADD	2.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.9% European (non-Finnish) · 718,210/1,179,946 alleles

Filtering AF 60.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.7%

Overall 59.2% 954,515/1,613,390 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	77.1%	1
Finnishnot grpmax-eligible	65.7%	2
Ashkenazi Jewishnot grpmax-eligible	61.3%	2
European (non-Finnish)grpmax	60.9%	2
Middle Eastern	60.5%	2
Remaining individualsnot grpmax-eligible	58.7%	2
South Asian	58%	2
Admixed American	47.7%	2
East Asian	45.6%	2
African / African-American	44.6%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: B3GNT8
Protein: p.Val188=
Coding: c.564G>A
MANE Select: NM_001009905 · reported on NM_001385648
dbSNP: rs284661
Type: single nucleotide variant
Location: chr19:41426215 (GRCh38)
Structure: AlphaFold pLDDT 96.05

Full B3GNT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

B3GNTL1 p.Gln144Arg Uncertain significance ★★ ⚠ same type
B3GNT8 c.-32-113C>T Benign ★★ same type
B3GNT8 c.-32-43A>G Benign ★★ same type
B3GNT8 c.*7T>C Benign ★★ same type
B3GNT8 p.Ala200= Benign ★★ same type
B3GNT8 p.Glu24= Benign ★★ same type
B3GNT8 p.Leu131= Benign ★★ same type
B3GNT8 p.Ser137Gly Benign ★★ ⚠ 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/b3gnt8-p-val188 (accessed [today's date]).

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