Is GALNT2 p.Pro181Ser (c.541C>T) pathogenic?

GALNT2 p.Pro181Ser (c.541C>T) is classified Uncertain significance in GALNT2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.0022%, sas); Associated with congenital disorder of glycosylation, type iit.

What condition is associated with GALNT2 p.Pro181Ser (c.541C>T)?

GALNT2 p.Pro181Ser (c.541C>T) is associated with congenital disorder of glycosylation, type iit (ClinVar).

How common is GALNT2 p.Pro181Ser (c.541C>T) in the general population?

GALNT2 p.Pro181Ser (c.541C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about GALNT2 p.Pro181Ser (c.541C>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

GALNT2 p.Pro181Ser

c.541C>T · VCV4077147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation, type iit

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -10.62	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 1.8	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.73	unconstrained · MANE · 195 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	22.0	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 0.0022% South Asian · 2/91,068 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,814 alleles · very rare exomes 11/1,461,544 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,534
European (non-Finnish)	0.000763%	131,079

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.Pro181Ser
Coding: c.541C>T
MANE Select: NM_004481
Type: single nucleotide variant
Location: chr1:230236420 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 90.27 · 13 PDB
Residue 181: the 'catalytic subdomain a' region

Full GALNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation, type iit — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GALNT2 p.Arg200Ter Pathogenic ★★ same condition
GALNT2 p.His359= Benign/Likely benign ★★ same condition
GALNT2 p.Arg208Gln Likely pathogenic ★ same condition
GALNT2 p.Arg210Pro Likely pathogenic ★ same condition
GALNT2 p.Gln289Ter Pathogenic ★ same condition
GALNT2 p.Glu231Ter Likely pathogenic ★ same condition
GALNT2 p.Phe104Ser Likely pathogenic ★ same condition
GALNT2 p.Arg154Trp 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-pro181ser (accessed [today's date]).

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