Is GALC p.Ser7Pro (c.19T>C) pathogenic?

GALC p.Ser7Pro (c.19T>C) is classified Uncertain significance in GALC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-24). AlphaMissense: likely benign (0.063); Very rare (popmax 0.00134%, afr); Associated with Krabbe disease.

What condition is associated with GALC p.Ser7Pro (c.19T>C)?

GALC p.Ser7Pro (c.19T>C) is associated with Krabbe disease (ClinVar).

How common is GALC p.Ser7Pro (c.19T>C) in the general population?

GALC p.Ser7Pro (c.19T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Krabbe disease inherited?

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

What do computational predictors say about GALC p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely benign (score 0.063) — an in-silico prediction, not a clinical call.

GALC p.Ser7Pro

c.19T>C · rs1887304079 · VCV3098026

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Krabbe disease

Computational evidence

Protein change
AlphaMissense	0.063	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 58 kb · p 0.37 · regional, not allelic
Overall
CADD	1.149	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,542 alleles

Overall 6.98e-05% 1/1,431,884 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: GALC
Protein: p.Ser7Pro
Coding: c.19T>C
MANE Select: NM_000153
dbSNP: rs1887304079
Type: single nucleotide variant
Location: chr14:87993146 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.56

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

Disease context

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

For Krabbe disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

GALC p.Ser7= Likely benign ★ same residue
GALC p.Ser7fs Pathogenic/Likely pathogenic ★★ same residue
GALC c.1033+1G>A Likely pathogenic ★★ same condition
GALC c.1034-1G>C Pathogenic/Likely pathogenic ★★ same condition
GALC c.1034-2A>G Pathogenic/Likely pathogenic ★★ same condition
GALC c.1161+2T>A Likely pathogenic ★★ same condition
GALC c.1251+1G>C Pathogenic/Likely pathogenic ★★ same condition
GALC c.1252-1G>C 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/galc-p-ser7pro (accessed [today's date]).

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