Is GALC p.Ser236= (c.708C>T) pathogenic?

GALC p.Ser236= (c.708C>T) is classified Conflicting classifications of pathogenicity in GALC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0483%, amr); Associated with Krabbe disease.

What condition is associated with GALC p.Ser236= (c.708C>T)?

GALC p.Ser236= (c.708C>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Ser236= (c.708C>T) in the general population?

GALC p.Ser236= (c.708C>T) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Ser236=

c.708C>T · rs773666802 · VCV886503

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Conditions

Krabbe disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.9	GERP -4.8
Overall
CADD	0.427	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/59,998 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00273% 44/1,613,704 alleles · ultra-rare exomes 19/1,461,528 · genomes 25/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,069
Remaining individualsnot grpmax-eligible	0.0176%	5,680
African / African-American	0.00267%	37,463
South Asian	0.0011%	91,074
European (non-Finnish)	8.48e-05%	1,179,724

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.Ser236=
Coding: c.708C>T
MANE Select: NM_000153
dbSNP: rs773666802
Type: single nucleotide variant
Location: chr14:87976402 (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 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
GALC c.1338+1G>C Likely pathogenic ★★ same condition
GALC c.1671-1G>A 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-ser236 (accessed [today's date]).

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