Is GALNT2 p.Pro50Arg (c.149C>G) pathogenic?

GALNT2 p.Pro50Arg (c.149C>G) is classified Uncertain significance in GALNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.0908); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with GALNT2 p.Pro50Arg (c.149C>G)?

GALNT2 p.Pro50Arg (c.149C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GALNT2 p.Pro50Arg (c.149C>G) in the general population?

GALNT2 p.Pro50Arg (c.149C>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about GALNT2 p.Pro50Arg (c.149C>G)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

GALNT2 p.Pro50Arg

c.149C>G · rs994653305 · VCV2610916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.81	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 4.8	GERP 2.1, phastCons 0.99
Regional constraint	o/e 0.73	unconstrained · MANE · 195 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	20.2	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00217% 35/1,613,746 alleles · ultra-rare exomes 33/1,461,622 · genomes 2/152,124 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.00254%	39,329
Admixed American	0.00167%	59,976

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: GALNT2
Protein: p.Pro50Arg
Coding: c.149C>G
MANE Select: NM_004481
dbSNP: rs994653305
Type: single nucleotide variant
Location: chr1:230178240 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 90.27 · 13 PDB

Full GALNT2 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

GALNT2 c.1560+4C>T Uncertain significance ★★ same condition
GALNT2 p.Ala30Val Uncertain significance ★★ ⚠ same condition
GALNT2 p.Ala35Thr Uncertain significance ★★ ⚠ same condition
GALNT2 p.Arg128Gln Uncertain significance ★★ ⚠ same condition
GALNT2 p.Arg404Ile Uncertain significance ★★ ⚠ same condition
GALNT2 p.Arg502Gln Uncertain significance ★★ ⚠ same condition
GALNT2 p.Arg543His Uncertain significance ★★ ⚠ same condition
GALNT2 p.Glu526Lys 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/galnt2-p-pro50arg (accessed [today's date]).

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