Is GALNT3 p.Ile245Val (c.733A>G) pathogenic?

GALNT3 p.Ile245Val (c.733A>G) is classified Uncertain significance in GALNT3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0661); Ultra-rare (popmax 0.0792%, sas); Associated with Inborn genetic diseases.

What condition is associated with GALNT3 p.Ile245Val (c.733A>G)?

GALNT3 p.Ile245Val (c.733A>G) is associated with Inborn genetic diseases (ClinVar).

How common is GALNT3 p.Ile245Val (c.733A>G) in the general population?

GALNT3 p.Ile245Val (c.733A>G) is ultra-rare (popmax 0.0792%, sas) (gnomAD).

What do computational predictors say about GALNT3 p.Ile245Val (c.733A>G)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

GALNT3 p.Ile245Val

c.733A>G · rs568101004 · VCV197237

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0792%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.24	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 7.9	GERP 0.45, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 22 kb · p 0.075 · regional, not allelic
Overall
CADD	21.3	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 0.0792% South Asian · 72/90,866 alleles

Filtering AF 0.0644% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0591%

Overall 0.00512% 82/1,601,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0792%	1,262
Remaining individualsnot grpmax-eligible	0.00644%	15,516
European (non-Finnish)	0.000513%	194,819

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: GALNT3
Protein: p.Ile245Val
Coding: c.733A>G
MANE Select: NM_004482
dbSNP: rs568101004
Type: single nucleotide variant
Location: chr2:165762010 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88
Residue 245: a UniProt-annotated variant site (in hftc1); the 'catalytic subdomain a' region

Full GALNT3 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

Similar variants

GALNT3 p.Ile245Thr Uncertain significance ★★ ⚠ same residue
GALNT3 p.Ala292Thr Uncertain significance ★★ ⚠ same condition
GALNT3 p.Arg261Gly Uncertain significance ★★ ⚠ same condition
GALNT3 p.Asn523Asp Uncertain significance ★★ ⚠ same condition
GALNT3 p.Asn72Ser Uncertain significance ★★ ⚠ same condition
GALNT3 p.Asp229Val Uncertain significance ★★ ⚠ same condition
GALNT3 p.Asp310Asn Uncertain significance ★★ ⚠ same condition
GALNT3 p.Glu49Asp 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/galnt3-p-ile245val (accessed [today's date]).

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