Is GALC p.Val247Phe (c.739G>T) pathogenic?

GALC p.Val247Phe (c.739G>T) is classified Likely pathogenic in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-17). AlphaMissense: ambiguous (0.4434); Absent from gnomAD v4.1; Associated with Krabbe disease.

What condition is associated with GALC p.Val247Phe (c.739G>T)?

GALC p.Val247Phe (c.739G>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Val247Phe (c.739G>T) in the general population?

GALC p.Val247Phe (c.739G>T) is absent from gnomAD v4.1 (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.Val247Phe (c.739G>T)?

AlphaMissense predicts ambiguous (score 0.4434) — an in-silico prediction, not a clinical call.

GALC p.Val247Phe

c.739G>T · rs2140016089 · VCV1077097

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4434 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Krabbe disease

Computational evidence

Protein change
AlphaMissense	0.4434	ambiguous
REVEL	0.583	indeterminate
SaProt	LLR -16.16	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -4.7
Regional constraint	o/e 1.03	unconstrained · MANE · 58 kb · p 0.37 · regional, not allelic
Overall
CADD	7.594	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: GALC
Protein: p.Val247Phe
Coding: c.739G>T
MANE Select: NM_000153
dbSNP: rs2140016089
Type: single nucleotide variant
Location: chr14:87976371 (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-val247phe (accessed [today's date]).

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