Is CSGALNACT1 p.Pro384Arg (c.1151C>G) pathogenic?

CSGALNACT1 p.Pro384Arg (c.1151C>G) is classified Conflicting classifications of pathogenicity in CSGALNACT1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.9972); Very rare (popmax 0.000595%, nfe); Associated with skeletal dysplasia, mild, with joint laxity and advanced bone age.

What condition is associated with CSGALNACT1 p.Pro384Arg (c.1151C>G)?

CSGALNACT1 p.Pro384Arg (c.1151C>G) is associated with skeletal dysplasia, mild, with joint laxity and advanced bone age (ClinVar).

How common is CSGALNACT1 p.Pro384Arg (c.1151C>G) in the general population?

CSGALNACT1 p.Pro384Arg (c.1151C>G) is very rare (popmax 0.000595%, nfe) (gnomAD).

What do computational predictors say about CSGALNACT1 p.Pro384Arg (c.1151C>G)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

CSGALNACT1 p.Pro384Arg

c.1151C>G · rs746391651 · VCV870477

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000595%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

skeletal dysplasia, mild, with joint laxity and advanced bone age

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 2% in CSGALNACT1
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -18.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	33.0	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 0.000595% European (non-Finnish) · 7/1,177,332 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000435% 7/1,611,014 alleles · very rare

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: CSGALNACT1
Protein: p.Pro384Arg
Coding: c.1151C>G
MANE Select: NM_001354483
dbSNP: rs746391651
Type: single nucleotide variant
Location: chr8:19418732 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71
Residue 384: a UniProt-annotated variant site (in sdjlaba; loss of galnac-transferase activity)

Full CSGALNACT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

skeletal dysplasia, mild, with joint laxity and advanced bone age — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSGALNACT1 p.Pro384= Likely benign ★ same residue
CSGALNACT1 p.Asn264Ser Likely pathogenic ★★ ⚠ same condition
CSGALNACT1 c.634+5G>C Uncertain significance ★★ same condition
CSGALNACT1 p.Asp219Glu Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Ile463Thr Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.His234= Benign ★★ same condition
CSGALNACT1 p.Phe473Tyr Benign/Likely benign ★★ same condition
CSGALNACT1 p.Ser193Asn Benign ★★ 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/csgalnact1-p-pro384arg (accessed [today's date]).

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