Is GALNT2 p.Ser158= (c.474C>T) pathogenic?

GALNT2 p.Ser158= (c.474C>T) is classified Likely benign in GALNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Ultra-rare (popmax 0.0214%, afr); Associated with Inborn genetic diseases.

What condition is associated with GALNT2 p.Ser158= (c.474C>T)?

GALNT2 p.Ser158= (c.474C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GALNT2 p.Ser158= (c.474C>T) in the general population?

GALNT2 p.Ser158= (c.474C>T) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

GALNT2 p.Ser158=

c.474C>T · VCV3518572

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -3.8
Overall
CADD	0.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,872 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00143% 23/1,613,292 alleles · ultra-rare exomes 9/1,461,156 · genomes 14/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,680
Admixed American	0.00334%	29,958
Remaining individualsnot grpmax-eligible	0.0032%	31,216
European (non-Finnish)	0.000254%	393,182

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.Ser158=
Coding: c.474C>T
MANE Select: NM_004481
Type: single nucleotide variant
Location: chr1:230236353 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 90.27 · 13 PDB
Residue 158: an α-helix; the 'catalytic subdomain a' region

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-ser158 (accessed [today's date]).

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