Is GALT p.Arg259= (c.777G>A) pathogenic?

GALT p.Arg259= (c.777G>A) is classified Likely benign in GALT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-11). Very rare (popmax 0.00441%, nfe); Associated with classic galactosemia.

What condition is associated with GALT p.Arg259= (c.777G>A)?

GALT p.Arg259= (c.777G>A) is associated with classic galactosemia (ClinVar).

How common is GALT p.Arg259= (c.777G>A) in the general population?

GALT p.Arg259= (c.777G>A) is very rare (popmax 0.00441%, nfe) (gnomAD).

How is Classic galactosemia inherited?

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

GALT p.Arg259=

c.777G>A · rs111033761 · VCV1622548

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Conditions

classic galactosemia

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 0.58	GERP -3.7, phastCons 0.99
Overall
CADD	6.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% European (non-Finnish) · 52/1,180,032 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00329% 53/1,613,168 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
African / African-American	0.00134%	74,900

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.Arg259=
Coding: c.777G>A
MANE Select: NM_000155
dbSNP: rs111033761
Type: single nucleotide variant
Location: chr9:34648851 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.08 · 2 PDB
Residue 259: a UniProt-annotated variant site (in galac1; loss of activity); a UniProt-annotated variant site (in galac1; mild); a β-strand

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.Arg259Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
GALT p.Arg259Trp Pathogenic/Likely pathogenic ★★ ⚠ 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-arg259 (accessed [today's date]).

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