Is GALNT3 p.Ser124Pro (c.370T>C) pathogenic?

GALNT3 p.Ser124Pro (c.370T>C) is classified Uncertain significance in GALNT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). AlphaMissense: likely pathogenic (0.6747); Very rare (popmax 0.00167%, amr); Associated with tumoral calcinosis, hyperphosphatemic, familial, 1.

What condition is associated with GALNT3 p.Ser124Pro (c.370T>C)?

GALNT3 p.Ser124Pro (c.370T>C) is associated with tumoral calcinosis, hyperphosphatemic, familial, 1 (ClinVar).

How common is GALNT3 p.Ser124Pro (c.370T>C) in the general population?

GALNT3 p.Ser124Pro (c.370T>C) is very rare (popmax 0.00167%, amr) (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.Ser124Pro (c.370T>C)?

AlphaMissense predicts likely pathogenic (score 0.6747) — an in-silico prediction, not a clinical call.

GALNT3 p.Ser124Pro

c.370T>C · VCV3584575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tumoral calcinosis, hyperphosphatemic, familial, 1

Computational evidence

Protein change
AlphaMissense	0.6747	likely pathogenic
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 5.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 22 kb · p 0.075 · regional, not allelic
Overall
CADD	22.7	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 · 1/60,018 alleles

Overall 6.2e-05% 1/1,614,158 alleles · very rare exomes 1/1,461,888 · genomes 0/152,270 · joint denominator

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.Ser124Pro
Coding: c.370T>C
MANE Select: NM_004482
Type: single nucleotide variant
Location: chr2:165770331 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88

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 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
GALNT3 c.689-2A>G Likely pathogenic ★★ same condition
GALNT3 p.Arg162Ter 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-ser124pro (accessed [today's date]).

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