Is GAL p.Ser19Pro (c.55T>C) pathogenic?

GAL p.Ser19Pro (c.55T>C) is classified Uncertain significance in GAL (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-14). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.000255%, nfe); Associated with familial temporal lobe epilepsy 8.

What condition is associated with GAL p.Ser19Pro (c.55T>C)?

GAL p.Ser19Pro (c.55T>C) is associated with familial temporal lobe epilepsy 8 (ClinVar).

How common is GAL p.Ser19Pro (c.55T>C) in the general population?

GAL p.Ser19Pro (c.55T>C) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about GAL p.Ser19Pro (c.55T>C)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

GAL p.Ser19Pro

c.55T>C · rs746008445 · VCV475916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial temporal lobe epilepsy 8

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -9.42	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 -1.2
Overall
CADD	11.94	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 0.000255% European (non-Finnish) · 3/1,176,832 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,606,698 alleles · very rare exomes 3/1,454,378 · genomes 0/152,320 · 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: GAL
Protein: p.Ser19Pro
Coding: c.55T>C
MANE Select: NM_015973
dbSNP: rs746008445
Type: single nucleotide variant
Location: chr11:68684978 (GRCh38)
Structure: AlphaFold pLDDT 66.71

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

Disease context

familial temporal lobe epilepsy 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GAL p.Ala10Thr Uncertain significance ★★ ⚠ same condition
GAL p.Ala15Thr Uncertain significance ★★ ⚠ same condition
GAL p.Arg67Trp Uncertain significance ★★ ⚠ same condition
GAL p.Arg88His Uncertain significance ★★ ⚠ same condition
GAL p.Asp106Asn Uncertain significance ★★ ⚠ same condition
GAL p.Asp106His Uncertain significance ★★ ⚠ same condition
GAL p.Glu69Lys Uncertain significance ★★ ⚠ same condition
GAL p.Leu60Phe Uncertain significance ★★ ⚠ 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/gal-p-ser19pro (accessed [today's date]).

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