Is B3GLCT p.Val61Ile (c.181G>A) pathogenic?

B3GLCT p.Val61Ile (c.181G>A) is classified Uncertain significance in B3GLCT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0695%, afr); Associated with Inborn genetic diseases.

What condition is associated with B3GLCT p.Val61Ile (c.181G>A)?

B3GLCT p.Val61Ile (c.181G>A) is associated with Inborn genetic diseases, Peters plus syndrome (ClinVar).

How common is B3GLCT p.Val61Ile (c.181G>A) in the general population?

B3GLCT p.Val61Ile (c.181G>A) is ultra-rare (popmax 0.0695%, afr) (gnomAD).

What do computational predictors say about B3GLCT p.Val61Ile (c.181G>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

B3GLCT p.Val61Ile

c.181G>A · rs375667011 · VCV497890

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0695%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0695% African / African-American · 52/74,824 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.049%

Overall 0.00982% 158/1,608,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0695%	1,439
Admixed American	0.0167%	5,998
Remaining individualsnot grpmax-eligible	0.016%	6,232
Finnishnot grpmax-eligible	0.011%	9,132
European (non-Finnish)	0.00647%	15,464
East Asian	0.00446%	22,423
South Asian	0.0011%	90,938

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: B3GLCT
Protein: p.Val61Ile
Coding: c.181G>A
MANE Select: NM_194318
dbSNP: rs375667011
Type: single nucleotide variant
Location: chr13:31229205 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB

Full B3GLCT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Peters plus syndrome

Similar variants

B3GLCT c.459+1G>A Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.660+1G>A Pathogenic ★★ same condition
B3GLCT p.Tyr380Ter Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.*1752C>T Uncertain significance ★★ same condition
B3GLCT p.Arg377His Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asn243Ser Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Asn Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Tyr Uncertain significance ★★ ⚠ same condition

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/b3glct-p-val61ile (accessed [today's date]).

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