Is GALT p.Pro295Ser (c.883C>T) pathogenic?

GALT p.Pro295Ser (c.883C>T) is classified Likely pathogenic in GALT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely pathogenic (0.7477); Very rare (popmax 0.00223%, eas); Associated with classic galactosemia.

What condition is associated with GALT p.Pro295Ser (c.883C>T)?

GALT p.Pro295Ser (c.883C>T) is associated with classic galactosemia (ClinVar).

How common is GALT p.Pro295Ser (c.883C>T) in the general population?

GALT p.Pro295Ser (c.883C>T) is very rare (popmax 0.00223%, eas) (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.Pro295Ser (c.883C>T)?

AlphaMissense predicts likely pathogenic (score 0.7477) — an in-silico prediction, not a clinical call.

GALT p.Pro295Ser

c.883C>T · rs111033783 · VCV2958532

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

classic galactosemia

Computational evidence

Protein change
AlphaMissense	0.7477	likely pathogenic ✓ concordant with ClinVar
REVEL	0.957	strongly pathogenic-leaning
SaProt	LLR -12.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,741 bp · p 6.8e-05 · regional, not allelic
Overall
CADD	25.3	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 0.00223% East Asian · 1/44,882 alleles

Overall 6.2e-05% 1/1,614,150 alleles · very rare exomes 1/1,461,856 · genomes 0/152,294 · joint denominator

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: GALT
Protein: p.Pro295Ser
Coding: c.883C>T
MANE Select: NM_000155
dbSNP: rs111033783
Type: single nucleotide variant
Location: chr9:34649060 (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.Pro295Thr Pathogenic/Likely pathogenic ★★ same residue
GALT p.Pro295_Tyr296insMetAlaSerPhePro Uncertain significance ★★ same residue
GALT p.Pro295= 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

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-pro295ser (accessed [today's date]).

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