Is GALT p.Pro100Arg (c.299C>G) pathogenic?

GALT p.Pro100Arg (c.299C>G) is classified Conflicting classifications of pathogenicity in GALT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.7025); Absent from gnomAD v4.1; Associated with classic galactosemia.

What condition is associated with GALT p.Pro100Arg (c.299C>G)?

GALT p.Pro100Arg (c.299C>G) is associated with classic galactosemia (ClinVar).

How common is GALT p.Pro100Arg (c.299C>G) in the general population?

GALT p.Pro100Arg (c.299C>G) is absent from gnomAD v4.1 (gnomAD).

How is Classic galactosemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about GALT p.Pro100Arg (c.299C>G)?

AlphaMissense predicts likely pathogenic (score 0.7025) — an in-silico prediction, not a clinical call.

GALT p.Pro100Arg

c.299C>G · rs1057524572 · VCV392632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

classic galactosemia

Computational evidence

Protein change
AlphaMissense	0.7025	likely pathogenic
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,741 bp · p 6.8e-05 · regional, not allelic
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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GALT
Protein: p.Pro100Arg
Coding: c.299C>G
MANE Select: NM_000155
dbSNP: rs1057524572
Type: single nucleotide variant
Location: chr9:34647538 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.08 · 2 PDB

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

Disease context

classic galactosemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Classic galactosemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

GALT p.Pro100Ala Uncertain significance ★ ⚠ same residue
GALT p.Pro100= Likely benign ★ same residue
GALT c.1060-1G>A Pathogenic/Likely pathogenic ★★ same condition
GALT c.252+1G>A Pathogenic ★★ same condition
GALT c.253-1G>A Pathogenic/Likely pathogenic ★★ same condition
GALT c.253-2A>G Pathogenic ★★ same condition
GALT c.328+2T>G Pathogenic/Likely pathogenic ★★ same condition
GALT c.329-2A>C Pathogenic ★★ 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/galt-p-pro100arg (accessed [today's date]).

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