Is GAL p.Ala22= (c.66G>A) pathogenic?

GAL p.Ala22= (c.66G>A) is classified Likely benign in GAL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-06). Ultra-rare (popmax 0.0522%, afr); Associated with familial temporal lobe epilepsy 8.

What condition is associated with GAL p.Ala22= (c.66G>A)?

GAL p.Ala22= (c.66G>A) is associated with familial temporal lobe epilepsy 8 (ClinVar).

How common is GAL p.Ala22= (c.66G>A) in the general population?

GAL p.Ala22= (c.66G>A) is ultra-rare (popmax 0.0522%, afr) (gnomAD).

GAL p.Ala22=

c.66G>A · rs542684427 · VCV475917

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0522%, afr)

Conditions

familial temporal lobe epilepsy 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.8, phastCons 0.99
Overall
CADD	8.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0522% African / African-American · 39/74,764 alleles

Filtering AF 0.0392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.00275% 44/1,602,084 alleles · ultra-rare exomes 20/1,449,744 · genomes 24/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0522%	1,917
Remaining individualsnot grpmax-eligible	0.00484%	20,663
Admixed American	0.00169%	59,212
European (non-Finnish)	8.52e-05%	1,174,244

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.Ala22=
Coding: c.66G>A
MANE Select: NM_015973
dbSNP: rs542684427
Type: single nucleotide variant
Location: chr11:68684989 (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-ala22 (accessed [today's date]).

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