Is GALNT12 p.Pro63Gln (c.188C>A) pathogenic?

GALNT12 p.Pro63Gln (c.188C>A) is classified Uncertain significance in GALNT12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.2912); Ultra-rare (popmax 0.0149%, eas).

How common is GALNT12 p.Pro63Gln (c.188C>A) in the general population?

GALNT12 p.Pro63Gln (c.188C>A) is ultra-rare (popmax 0.0149%, eas) (gnomAD).

What do computational predictors say about GALNT12 p.Pro63Gln (c.188C>A)?

AlphaMissense predicts likely benign (score 0.2912) — an in-silico prediction, not a clinical call.

GALNT12 p.Pro63Gln

c.188C>A · rs1481280788 · VCV485658

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2912 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2912	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -14.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.23, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 228 bp · p 0.44 · regional, not allelic
Overall
CADD	22.2	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 0.0149% East Asian · 3/20,170 alleles

Filtering AF 0.00403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00209%

Overall 0.000272% 3/1,103,028 alleles · ultra-rare exomes 2/955,076 · genomes 1/147,952 · 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: GALNT12
Protein: p.Pro63Gln
Coding: c.188C>A
MANE Select: NM_024642
dbSNP: rs1481280788
Type: single nucleotide variant
Location: chr9:98807886 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 93.84 · 1 PDB
Residue 63: a β-strand; the 'disordered' region

Full GALNT12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GALNT12 p.Pro63= Benign/Likely benign ★★ same residue
GALNT12 p.Pro63Arg Uncertain significance ★ ⚠ same residue
GALNT12 p.Pro63Leu Uncertain significance ★ ⚠ same residue
GALNT12 c.1036-3C>T Uncertain significance ★★ same type
GALNT12 c.1212+1G>T Uncertain significance ★★ same type
GALNT12 c.1213-3C>T Uncertain significance ★★ same type
GALNT12 c.1344+4A>C Uncertain significance ★★ same type
GALNT12 c.732-5T>G Uncertain significance ★★ 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/galnt12-p-pro63gln (accessed [today's date]).

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