Is GALNT3 p.Ser341Pro (c.1021T>C) pathogenic?

GALNT3 p.Ser341Pro (c.1021T>C) is classified Uncertain significance in GALNT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-15). AlphaMissense: likely benign (0.0923); Absent from gnomAD v4.1; Associated with tumoral calcinosis, hyperphosphatemic, familial, 1.

What condition is associated with GALNT3 p.Ser341Pro (c.1021T>C)?

GALNT3 p.Ser341Pro (c.1021T>C) is associated with tumoral calcinosis, hyperphosphatemic, familial, 1 (ClinVar).

How common is GALNT3 p.Ser341Pro (c.1021T>C) in the general population?

GALNT3 p.Ser341Pro (c.1021T>C) is absent from gnomAD v4.1 (gnomAD).

How is Familial tumoral calcinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about GALNT3 p.Ser341Pro (c.1021T>C)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

GALNT3 p.Ser341Pro

c.1021T>C · VCV3584560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tumoral calcinosis, hyperphosphatemic, familial, 1

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.36	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 3.2	GERP -5.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 22 kb · p 0.075 · regional, not allelic
Overall
CADD	16.01	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GALNT3
Protein: p.Ser341Pro
Coding: c.1021T>C
MANE Select: NM_004482
Type: single nucleotide variant
Location: chr2:165759388 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88
Residue 341: a UniProt-annotated variant site (in hftc1)

Full GALNT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tumoral calcinosis, hyperphosphatemic, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial tumoral calcinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

GALNT3 p.Ser341= Likely benign ★ same residue
GALNT3 p.Ser341Leu Uncertain significance ⚠ same residue
GALNT3 c.1074-1G>C Likely pathogenic ★★ same condition
GALNT3 c.1524+1G>A Pathogenic ★★ same condition
GALNT3 c.1524+5G>A Pathogenic ★★ same condition
GALNT3 c.1626+1G>A Pathogenic ★★ same condition
GALNT3 c.516-2A>G Pathogenic/Likely pathogenic ★★ same condition
GALNT3 c.516-2A>T Pathogenic ★★ 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-ser341pro (accessed [today's date]).

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