Is GAL p.Ser123Phe (c.368C>T) pathogenic?

GAL p.Ser123Phe (c.368C>T) is classified Uncertain significance in GAL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-13). AlphaMissense: likely benign (0.2913); Ultra-rare (popmax 0.0424%, eas); Associated with familial temporal lobe epilepsy 8.

What condition is associated with GAL p.Ser123Phe (c.368C>T)?

GAL p.Ser123Phe (c.368C>T) is associated with familial temporal lobe epilepsy 8 (ClinVar).

How common is GAL p.Ser123Phe (c.368C>T) in the general population?

GAL p.Ser123Phe (c.368C>T) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

What do computational predictors say about GAL p.Ser123Phe (c.368C>T)?

AlphaMissense predicts likely benign (score 0.2913) — an in-silico prediction, not a clinical call.

GAL p.Ser123Phe

c.368C>T · rs747411981 · VCV940511

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial temporal lobe epilepsy 8

Computational evidence

Protein change
AlphaMissense	0.2913	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.41	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 1.5	GERP 0.47, phastCons 0.85
Overall
CADD	22.1	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 0.0424% East Asian · 19/44,848 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00168% 27/1,606,256 alleles · ultra-rare exomes 25/1,453,946 · genomes 2/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0424%	2,360
Remaining individualsnot grpmax-eligible	0.00161%	62,252
African / African-American	0.00133%	74,908
South Asian	0.0011%	90,956
European (non-Finnish)	0.000426%	234,591

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.Ser123Phe
Coding: c.368C>T
MANE Select: NM_015973
dbSNP: rs747411981
Type: single nucleotide variant
Location: chr11:68690983 (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-ser123phe (accessed [today's date]).

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